Increased concentrations of tumour necrosis factor in "cachectic" patients with severe chronic heart failure.
To ascertain whether patients with cardiac failure and reduced body weight ("cardiac cachexia") have increased circulating concentrations of tumour necrosis factor (cachectin). Patients with cardiac failure were prospectively identified as "cachectic" (body fat less than 27% in men and less than 29% in women measured by skinfold thickness callipers) or "non-cachectic". Tumour necrosis factor was assayed blind to patient group. Cardiology unit in a tertiary referral centre. 26 consecutive patients (10 women) (mean age 61) admitted for investigation or treatment of chronic heart failure. All were in New York Heart Association class III or IV. In nine of the 16 cachectic patients the concentration of tumour necrosis factor was increased (mean (SEM) 74 (20) pg/ml) compared with one of the 10 "non-cachectic" patients (22 pg/ml, p less than 0.001). Patients with a raised circulating concentration of tumour necrosis factor weighed significantly less (55.6 (3.5) kg) than those in whom the concentration of tumour necrosis factor was normal (69.0 (4.1) kg) (p = 0.02). Circulating concentrations of tumour necrosis factor were increased in a significant proportion of patients with chronic heart failure and low body weight. Tumour necrosis factor stimulates catabolism experimentally and it may be a factor in the weight loss seen in patients with "cardiac cachexia".


[Sexuality and depression among pregnant women with recurrent spontaneous abortion].
It was to compare pregnant women who experienced recurrent spontaneous abortion (RSA) and those who did not in terms of the prevalence of depressive symptoms and sexual behavior. A prospective case-control study was carried out. The first group consisted of women with RSA and the second, of primigravidae. The Beck Depression Inventory (BDI), the Female Sexual Function Index (FSFI) and one more questionnaire, developed by the authors themselves, about emotional aspects resulting from sexual intercourse during pregnancy were applied. The Student t-test was used to compare quantitative variables with normal distribution, and categorical variables were compared by the chi-square test or Fisher's exact test. The level of significance was set at p<0.05. The BDI showed (19.9 versus 10.0%) approximately twice the incidence of depression in the RSA group. Regarding sexual function, the average scores of the FSFI were 21.1 and 16.4 (p<0.05) for the study and control groups, respectively, although no significant difference was observed only in the desire domain (average 3.4±1.3 for the RSA group and 3.7±1.1 for control group) (p=0.1). We observed that, regardless the presence or absence of an RSA history among the pregnant women, the higher the depression score, the lower the sexuality score (r=-0,3). The RSA pregnant group often experiences twice higher depression and more impaired sexual function. There is an inverse association between depression and sexual function.


Nonconservative higher-order hydrodynamic modulation instability.
The modulation instability (MI) is a universal mechanism that is responsible for the disintegration of weakly nonlinear narrow-banded wave fields and the emergence of localized extreme events in dispersive media. The instability dynamics is naturally triggered, when unstable energy sidebands located around the main energy peak are excited and then follow an exponential growth law. As a consequence of four wave mixing effect, these primary sidebands generate an infinite number of additional sidebands, forming a triangular sideband cascade. After saturation, it is expected that the system experiences a return to initial conditions followed by a spectral recurrence dynamics. Much complex nonlinear wave field motion is expected, when the secondary or successive sideband pair that is created is also located in the finite instability gain range around the main carrier frequency peak. This latter process is referred to as higher-order MI. We report a numerical and experimental study that confirms observation of higher-order MI dynamics in water waves. Furthermore, we show that the presence of weak dissipation may counterintuitively enhance wave focusing in the second recurrent cycle of wave amplification. The interdisciplinary weakly nonlinear approach in addressing the evolution of unstable nonlinear waves dynamics may find significant resonance in other nonlinear dispersive media in physics, such as optics, solids, superfluids, and plasma.


JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factor-stimulated vascular smooth muscle cells.
The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na(+)-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE.


Phosphorus-modified bone chars with developed porosity for efficient removal of Pb(II), Cu(II), and Cd(II).
Guided by the concept of treating the wastes with wastes, the efficient use of bone residuals as separation materials is worthy of study. Since bone chars (BCs) are composed of hydroxyapatite and carbon matrix, it is desired to extend the carbon component with improved pore structure and abundant modified groups further, which is favorable to capture metal ions. In this work, phosphorus-modified BCs (PBCs) were fabricated by pretreating bone residuals with phytic acid, achieving improved surface areas (208.7-517.6 m2/g, 37.9-8.2-fold of enhancement) and abundant surface phosphorus contents (5.63-7.54 at.%, 2.8-5.8-fold of enhancement) than BCs. PBCs could adsorb heavy metals with fast kinetics (10.0 h) and excellent maximum capacities (463.9, 156.5, and 80.9 mg/g for Pb(II), Cu(II), and Cd(II)). Spectroscopic results demonstrated that the formation of precipitation was crucial for the enrichment of Pb(II). Moreover, the coordination with functional groups (O-/reductive N-species), the cation exchange with inorganic Ca2+, the electrostatic attraction with deprotonated O-, and the cation-π coordination should also be considered for the sorption. Our study facilitated the application of activated bone wastes as a promising candidate to remediate aquatic heavy metals.


Supercooled liquid sulfur maintained in three-dimensional current collector for high-performance Li-S batteries.
In lithium-sulfur (Li-S) chemistry, the electrically/ionically insulating nature of sulfur and Li2S leads to sluggish electron/ion transfer kinetics for sulfur species conversion. Sulfur and Li2S are recognized as solid at room temperature, and solid-liquid phase transitions are the limiting steps in Li-S batteries. Here, we visualize the distinct sulfur growth behaviors on Al, carbon, Ni current collectors and demonstrate that (i) liquid sulfur generated on Ni provides higher reversible capacity, faster kinetics, and better cycling life compared to solid sulfur; and (ii) Ni facilitates the phase transition (e.g., Li2S decomposition). Accordingly, light-weight, 3D Ni-based current collector is designed to control the deposition and catalytic conversion of sulfur species toward high-performance Li-S batteries. This work provides insights on the critical role of the current collector in determining the physical state of sulfur and elucidates the correlation between sulfur state and battery performance, which will advance electrode designs in high-energy Li-S batteries.


Protein intake is positively associated with body cell mass in weight-stable HIV-infected men.
Depletion of body cell mass (BCM) in human immunodeficiency virus (HIV)-infected patients is strongly associated with disease progression and death. Although whole-body protein turnover is increased in HIV infection, it is not known whether protein intake is independently associated with BCM. The purpose of this study was to determine the associations, if any, between protein intake and several body composition variables in 467 weight-stable, HIV-infected men with CD4 <200 cells/mm(3) enrolled in a multicenter nutritional supplementation trial. Baseline BCM, total body fat and extracellular mass as measured by bioelectrical impedance analysis, dietary intake (24 h food recall) and muscle building activity assessed by structured interview were analyzed to determine association(s) between body composition variables and macronutrient intake. Multiple regression analysis showed that BCM was positively associated with body weight (P = 0.001), height (P < 0.001), protein intake (P < 0.001), muscle-building activity (P < 0.001) and African-American ethnicity (P < 0.05) and negatively associated with carbohydrate intake (P < 0.05), age (P < 0.001) and number of prior AIDS-related diagnoses (P < 0.001). We conclude that protein intake is associated with increased BCM, whereas carbohydrate intake is negatively associated with BCM in HIV-infected men, independently of muscle building activity.


Pulmonary preinvasive neoplasia.
Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology. Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment.


The role of ultrasonography in examination of the stability of Tile-B2 pelvic fractures: 7 case reports and a literature review.
Determining whether a Tile-B2 pelvic fracture is stable is very challenging. We sought to identify the role of ultrasonography in determining the stability of Tile-B2 pelvic fractures. We collected the clinical data of patients with Tile-B2 pelvic fractures who presented at Xi'an Hong-Hui Hospital between June 1, 2016, and August 5, 2016. The treatment strategy of each patient was determined by a team of senior surgeons in the department. A single sinologist observed the movement of the fracture sites in patients during rest, under compression, and during separation to determine fracture stability. According to the pelvic fracture stability assessment, an appropriate treatment strategy was redetermined. Overall, 7 patients, including 5 women and 2 men, with Tile-B2 pelvic fractures were included in this case series. During the initial examination, senior surgeons recommended that 2 patients should undergo internal fixation and 4 patients, conservative treatment; treatment was undecided for 1 patient. After ultrasonography examination, 4 patients underwent surgery via the Stoppa (n = 2) or ilioinguinal approach (n = 1) or cannulated screw fixation (n = 1). The rest of the patients (n = 3) received conventional treatment. Follow-up ranged from 6 to 10 months. Most of the patients showed excellent functions based on their last Majeed grading scores. There were no complications during the follow-up. Using ultrasonography examination, the preoperative treatment plan in 1 patient was changed, and the uncertain preoperative plan in 1 patient was identified. Preoperative assessment of stability using ultrasonography may assist surgeons in making appropriate treatment choices for patients with Tile-B2 pelvic fractures.


Religiosity in Acute Psychiatric Inpatients: Relationship With Demographics, Clinical Features, and Length of Stay.
This study examined the relationship between religiosity in 175 psychiatric inpatients as measured by the subscales of the Duke University Religion Index (DUREL) and sociodemographic (age, sex, and race), clinical (primary diagnosis, suicidality, and psychotic symptoms), and outcome (length of stay [LOS] and readmission rates) measures. Psychosis was assessed by Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scale. Bivariate and multivariate analyses were used to examine the association between the DUREL subscales and the outcome measures. High scorers on the nonorganized religiosity subscale were less likely to have psychosis (47% vs. 52%; p < 0.05) but had greater psychosis severity (mean ± SD, 14.5 ± 5 vs.12.4 ± 6; p < 0.05), as measured by the CRDPSS scale, and significantly longer LOS (mean ± SD, 8.3 ± 3.8 vs. 6.9 ± 3.4; p < 0.05). Conversely, they were less likely to report previous suicide attempts than low scorers (p < 0.05). These results suggest that a brief measure of religious activities may identify psychiatric inpatients at greater risk for psychosis, suicidality, and longer hospitalizations.


Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.
The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.


Anti-MUC1 antibodies and ovarian cancer risk: prospective data from the Nurses' Health Studies.
The surface epithelial glycoprotein MUC1 becomes overexpressed and hypoglycosylated in adenocarcinomas; similar changes occur during nonmalignant inflammatory events. Antibodies developed against tumor-like MUC1 in response to such events could be one way through which ovarian cancer risk factors operate. We evaluated the association between anti-MUC1 antibodies and risk of ovarian cancer in a prospective nested case-control study in the Nurses' Health Studies. We used an ELISA to measure plasma anti-MUC1 antibodies in 117 ovarian cancer cases collected at least 3 years before diagnosis and 339 matched controls. In controls, younger women (P-trend = 0.03), those with a tubal ligation (P = 0.03), and those with fewer ovulatory cycles (P-trend = 0.04) had higher antibody levels. In cases, women with late-stage disease (P = 0.04) and those whose specimen was >11 years remote from diagnosis (P = 0.01) had higher antibody levels. Overall, increasing anti-MUC1 antibody levels were associated with a nonsignificant trend for lower risk for ovarian cancer, but there was highly significant heterogeneity by age (P-heterogeneity = 0.005). In women <64 years, the antibody level in quartiles 2 to 4 versus quartile 1 were associated with reduced risk (relative risk = 0.53; 95% confidence interval, 0.31-0.93; P-trend = 0.03), whereas in women > or = 64 years, the corresponding relative risk was 2.11 (95% confidence interval, 0.73-6.04); P-trend = 0.05). Anti-MUC1 antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment. Key elements of an "immune model" to explain ovarian cancer risk factors are confirmed and should be evaluated in larger prospective studies.


Cystic fibrosis: a comparison of computed tomography and plain chest radiographs.
In patients with cystic fibrosis, plain chest radiographs may suggest the presence of bronchiectasis, bronchoceles, hilar adenopathy, or pulmonary arterial hypertension. We compared computed tomography (CT) with conventional chest radiography in 12 patients. CT clearly reveals the cause of increased linear markings, nodular lesions, and enlarged hila as seen on plain chest radiographs. It showed that nine patients had hilar adenopathy, five had enlarged pulmonary arteries, and 11 had bronchiectasis. Bronchoceles, a finding that may influence therapy, were seen on seven CT scans but on only four of the plain films.


Rotational motion in LiBH4/LiI solid solutions.
We investigated the localized rotational diffusion of the (BH(4))(-) anions in LiBH(4)/LiI solid solutions by means of quasielastic and inelastic neutron scattering. The (BH(4))(-) motions are thermally activated and characterized by activation energies in the order of 40 meV. Typical dwell times between jumps are in the picosecond range at temperatures of about 200 K. The motion is dominated by 90° reorientations around the 4-fold symmetry axis of the tetrahedraly shaped (BH(4))(-) ions. As compared to the pure system, the presence of iodide markedly reduces activation energies and increases the rotational frequencies by more than a factor of 100. The addition of iodide lowers the transition temperature, stabilizing the disordered high temperature phase well below room temperature.


Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia.
Skeletal dysplasia (SD) is one of the most common inherited neonatal disorders worldwide, where the recurrent pathogenic mutations in the FGFR2, FGFR3, COL1A1, COL1A2 and COL2A1 genes are frequently reported in both non-lethal and lethal SD. The traditional prenatal diagnosis of SD using ultrasonography suffers from lower accuracy and performed at latter gestational stage. Therefore, it remains in desperate need of precise and accurate prenatal diagnosis of SD in early pregnancy. With the advancements of next-generation sequencing (NGS) technology and bioinformatics analysis, it is feasible to develop a NGS-based assay to detect genetic defects in association with SD in the early pregnancy. An ampliseq-based targeted sequencing panel was designed to cover 87 recurrent hotspots reported in 11 common dominant SD and run on both Ion Proton and NextSeq550 instruments. Thirty-six cell-free and 23 genomic DNAs were used for assay developed. Spike-in DNA prepared from standard sample harboring known mutation and normal sample were also employed to validate the established SD workflow. Overall performances of coverage, uniformity, and on-target rate, and the detecting limitations on percentage of fetal fraction and read depth were evaluated. The established targeted-seq workflow enables a single-tube multiplex PCR for library construction and shows high amplification efficiency and robust reproducibility on both Ion Proton and NextSeq550 platforms. The workflow reaches 100% coverage and both uniformity and on-target rate are > 96%, indicating a high quality assay. Using spike-in DNA with different percentage of known FGFR3 mutation (c.1138 G > A), the targeted-seq workflow demonstrated the ability to detect low-frequency variant of 2.5% accurately. Finally, we obtained 100% sensitivity and 100% specificity in detecting target mutations using established SD panel. An expanded panel for rapid and cost-effective genetic detection of SD has been developed. The established targeted-seq workflow shows high accuracy to detect both germline and low-frequency variants. In addition, the workflow is flexible to be conducted in the majority of the NGS instruments and ready for routine clinical application. Taken together, we believe the established panel provides a promising diagnostic or therapeutic strategy for prenatal genetic testing of SD in routine clinical practice.


Validity and reliability of a novel measure of activity performance and participation.
To develop and evaluate an innovative clinician-rated measure, which produces global numerical ratings of activity performance and participation. Repeated measures study with 48 community-dwelling participants investigating clinical sensibility, comprehensiveness, practicality, inter-rater reliability, responsiveness, sensitivity and concurrent validity with Barthel Index. Important clinimetric characteristics including comprehensiveness and ease of use were rated >8/10 by clinicians. Inter-rater reliability was excellent on the summary scores (intraclass correlation of 0.95-0.98). There was good evidence that the new outcome measure distinguished between known high and low functional scoring groups, including both responsiveness to change and sensitivity at the same time point in numerous tests. Concurrent validity with the Barthel Index was fair to high (Spearman Rank Order Correlation 0.32-0.85, p > 0.05). The new measure's summary scores were nearly twice as responsive to change compared with the Barthel Index. Other more detailed data could also be generated by the new measure. The Activity Performance Measure is an innovative outcome instrument that showed good clinimetric qualities in this initial study. Some of the results were strong, given the sample size, and further trial and evaluation is appropriate. Implications for Rehabilitation The Activity Performance Measure is an innovative outcome measure covering activity performance and participation. In an initial evaluation, it showed good clinimetric qualities including responsiveness to change, sensitivity, practicality, clinical sensibility, item coverage, inter-rater reliability and concurrent validity with the Barthel Index. Further trial and evaluation is appropriate.


Mucosal healing and the risk of ischemic heart disease or atrial fibrillation in patients with celiac disease; a population-based study.
Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF. We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF. Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were ≥ 60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73-1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73-1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74-1.30). In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.


SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML.
KMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigation of SET expression in acute myeloid leukemia (AML) samples demonstrated that SET is overexpressed, and elevated expression of SET is correlated with poor prognosis and with the expression of MEIS and HOXA genes in AML patients. Silencing SET specifically abolished the clonogenic ability of KMT2A-R leukemic cells and the transcription of KMT2A targets genes HOXA9 and HOXA10. Subsequent mechanistic investigations showed that SET interacts with both KMT2A wild type and fusion proteins, and it is recruited to the HOXA10 promoter. Pharmacological inhibition of SET by FTY720 disrupted SET-PP2A interaction leading to cell cycle arrest and increased sensitivity to chemotherapy in KMT2A-R-leukemic models. Phospho-proteomic analyses revealed that FTY720 reduced the activity of kinases regulated by PP2A, including ERK1, GSK3β, AURB and PLK1 and led to suppression of MYC, supporting the hypothesis of a feedback loop among PP2A, AURB, PLK1, MYC, and SET. Our findings illustrate that SET is a novel player in KMT2A-R leukemia and they provide evidence that SET antagonism could serve as a novel strategy to treat this aggressive leukemia.


High-dose radioimmunotherapy combined with extracorporeal depletion in a syngeneic rat tumor model: evaluation of toxicity, therapeutic effect, and tumor model.
The aim of the current study was to investigate the possibility of increasing the maximal tolerated dose (MTD) of a tumor-selective radiolabeled antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated whether this increase in dose improved the therapeutic effect on solid manifest tumors in an immunocompetent animal model. Rats were injected with high activities/body weight of lutetium ((177)Lu)- or yttrium ((90)Y)-labeled antibody conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment 24 hours postinjection. Myelotoxicity was assessed by analysis of blood parameters for 12 weeks. The effect of increased doses in combination with extracorporeal affinity adsorption treatment was evaluated with respect to myelotoxicity and therapeutic effect in a syngeneic rat colon cancer model. The MTD of (177)Lu- or (90)Y-labeled immunoconjugates could be increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with (177)Lu- or (90)Y-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 x 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection. Extracorporeal affinity adsorption treatment is a method that safely and efficiently reduces myelotoxicity associated with RIT. Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. However, because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity in combination with extracorporeal affinity adsorption treatment in this study. Targeted RIT with beta-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease.


[Cytologic and morphologic characteristics of human papillomavirus infection in cervix uteri pathology].
The role of human papilloma virus (HPV) in genital cancer is not yet clear at present, but the available data testify to serious changes in cervix uteri epithelium in the process of its infection. Close correlation was demonstrated between HPV type specificity and the degree of epithelial morphological changes as well as histologic tumor variant, and its degree of differentiation. Interrelation between HPV type and level of both regression and progression of atypically changed cervix uteri epithelium is established. Cytomorphological method of the evaluation of cell koilocytotic atypia is the marker to diagnose HPV infection when screening a chosen woman population. The development and introducing of sensitive and reliable identification methods of type-specific DNA sequences of HPV infection in diagnostic material to form a low risk (HPV-6 and II types) and a high risk group (HPV-16 and 18 types) by malignancy of cervix uteri epithelium have considerable promise. It is advisable to study HPV role in the development of adenogenic tumors of uterine cervix and body.


[Ultrastructure of the skin in systemic scleroderma].
Biopsy specimens of the skin of the back of the forearm and hand in 20 patients with systemic scleroderma were studied using histological and electron microscopy methods. There were revealed evidences of intensified neofibrillogenesis, changes in collagen structures of the derma (destruction and defects of packing of collagenous fibrills, variability of their thickness in a fibre) and in the microcirculatory bed. In 18 out of 20 cases the nuclei of the connective-tissue cells and cells of the basal layer of the epidermis contained the so-called nuclear bodies, which are considered by a number of authors as an indirect evidence of a viral infection. The process of an intensified neoformation of collagen fibrils considerably predominated over destructive processes in collagen structures.


Endotoxicity associated with the Lyme disease Borrelia: recent findings.
The endotoxicity of Borrelia burgdorferi, the causative agent of Lyme Disease, a tick-borne spirochetosis, was studied using Limulus assay and pyrogen test in rabbit. Some suspensions of Ixodes ricinus and Ixodes dammini associated Borrelia were able to gelify Limulus lysate and demonstrated a febrile response in rabbit. These findings and other recent data demonstrating an endotoxin-like activity of the Lyme Disease agent are discussed in the context of the pathogenic mechanisms of the illness.


Effect of Early Administration of Vitamin D on Clinical Outcome in Critically Ill Sepsis Patients: A Randomized Placebo-controlled Trial.
Administration of vitamin D to unselected heterogeneous critically ill patients did not demonstrate outcome benefit. The current study was undertaken to identify if early administration of vitamin D can reduce intensive care unit (ICU) length of stay and improve clinical outcomes in critically ill patients with sepsis. This single-center randomized double-blind placebo-controlled trial was done in the ICU and emergency inpatient ward of a tertiary care teaching institute in New Delhi, India. A total of 126 adult patients aged 18 to 80 years of either sex diagnosed to have sepsis were included within 24 hours of admission to the hospital and randomized into vitamin D or placebo groups. The patients in the intervention group received vitamin D3 540,000 units dissolved in 45 mL of milk. The placebo group received 45 mL of milk. The median length of ICU stay (8 vs 9 days; p = 0.32), median length of hospital stay (12 vs 12 days; p = 0.33), median duration of vasopressors requirement (4 vs 3 days; p = 0.84), median duration of mechanical ventilation (5 vs 7 days; p = 0.23), requirement of tracheostomy (34 vs 39%; p = 0.71), and 90-day mortality [35 vs 46%; p = 0.29; HR 0.72 (0.42-1.24)] were similar in vitamin D and placebo arm.A subgroup analysis in patients with severe vitamin D deficiency (vitamin D <12 ng/mL) revealed a significantly decreased incidence of tracheostomy (28 vs 57%; p = 0.04), a trend toward decreased 90-day mortality [34 vs 66%; p = 0.08; HR 0.44 (0.19-1.01)], and duration of mechanical ventilation (6 vs 11 days; p = 0.05) in patients receiving vitamin D. Administration of large-dose vitamin D within 24 hours of admission does not reduce the length of ICU stay in critically ill sepsis patients. Bhattacharyya A, Subramaniam R, Baidya DK, Aggarwal P, Wig N. Effect of Early Administration of Vitamin D on Clinical Outcome in Critically Ill Sepsis Patients: A Randomized Placebo-controlled Trial. Indian J Crit Care Med 2021;25(10):1147-1154.


Sparse brain network recovery under compressed sensing.
Partial correlation is a useful connectivity measure for brain networks, especially, when it is needed to remove the confounding effects in highly correlated networks. Since it is difficult to estimate the exact partial correlation under the small- n large- p situation, a sparseness constraint is generally introduced. In this paper, we consider the sparse linear regression model with a l(1)-norm penalty, also known as the least absolute shrinkage and selection operator (LASSO), for estimating sparse brain connectivity. LASSO is a well-known decoding algorithm in the compressed sensing (CS). The CS theory states that LASSO can reconstruct the exact sparse signal even from a small set of noisy measurements. We briefly show that the penalized linear regression for partial correlation estimation is related to CS. It opens a new possibility that the proposed framework can be used for a sparse brain network recovery. As an illustration, we construct sparse brain networks of 97 regions of interest (ROIs) obtained from FDG-PET imaging data for the autism spectrum disorder (ASD) children and the pediatric control (PedCon) subjects. As validation, we check the network reproducibilities by leave-one-out cross validation and compare the clustered structures derived from the brain networks of ASD and PedCon.


[Electrocardiographic interval as a predictor of life-threatening arrhythmias in dilated cardiomyopathy patients].
The Tpe interval (Tp-e) in the surface electrocardiogram represents ventricular repolarization, a key phase in the pathogenesis of severe ventricular arrhythmias. However, there are few studies evaluating changes in this electrocardiographic interval as a risk factor for serious arrhythmias in patients with dilated cardiomyopathy. To determine whether the Tp-e interval prolongation predicts the presence of life-threatening arrhythmias in patients with dilated cardiomyopathy (DCM) with implantable cardioverter-defibrillator (ICD). Analytical, cross-sectional study in patients with DCM with ICDs. The Tp-e interval was measured in the V2 electrocardiographic lead and correlated with the incidence of life-threatening arrhythmias identified by the ICD. 53 patients were recruited, 10 (18.8%) presented life-threatening arrhythmias. Prolongation of Tp-e interval was related to an increase in the incidence of ventricular tachycardia/fibrillation tachycardia (VT/FT) with a mean of 93 ± 20.5 ms (p = 0.003), using ROC curves to determine the thereshold of 90 ms for increased risk of VT/VF with sensitivity of 70% and specificity of 84%, with an area under the curve of 0.798. The prolongation of the ITp-e interval greater than 90 ms in a population with dilated cardiomyopathy predicts the presence of arrhythmic episodes, such as VT and/or VT/FT.


Burden of disease: A scoping review of HIV/AIDS and TB in occupational noise-induced hearing loss.
Occupational noise-induced hearing loss (ONIHL) does not occur in isolation from other influencing factors such as health conditions and illnesses like human immunodeficiency virus and acquired immunodeficiency syndrome (HIV and AIDS), as well as tuberculosis (TB). How the burden of disease influences the occurrence and/or management of ONIHL becomes a key if the goal of hearing conservation programmes (HCPs) is to be achieved within these contexts. The purpose of this scoping review was to conduct an investigation on how the burden of disease's influence on ONIHL is reported in literature, with a specific focus on the most prevalent diseases in South African mines - HIV and AIDS and TB. A scoping review was conducted using the Arksey and O'Malley's framework. A search was conducted in five electronic bibliographic databases and the grey literature. The search procured 10 publications, with two specific to ONIHL within the South African context. In addition to the two publications specific to TB and ONIHL, findings revealed a serious gap in the evidence around the scoping review question globally. This obvious lack of investigations into the influence of these two conditions in the South African mining context raises serious implications about the responsiveness, and proactive nature of HCPs within this population. Considering the burden of diseases on otology and audiology is critical as certain diseases cause hearing impairment either as a primary effect, as a secondary/opportunistic effect or as a side effect of treatment options for that disease. An employee suffering from any such disease with concomitant exposure to hazardous noise levels presents an even bigger challenge to HCPs if such is not taken into consideration in the conception, implementation and monitoring of HCPs.


Monitoring cerebral perfusion using near-infrared spectroscopy and laser Doppler flowmetry.
This paper describes the simultaneous use of two, noninvasive, near-infrared techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser Doppler flow system (LDF) to measure changes in the blood oxygenation, blood concentration and blood flow velocity in the brain. A piglet was used as animal model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for achieving changes in the listed cerebrovascular parameters. The time courses of blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were found to correspond closely with those of carotid blood flow and arterial carbon dioxide pressure (PaCO2). This result shows the additional value of LDF when combined with NIRS, preferably in one instrument. Development of pulsed LDF for regional blood flow measurement is indicated.


Food and beverage purchases in corner stores, gas-marts, pharmacies and dollar stores.
Little is known about customer purchases of foods and beverages from small and non-traditional food retailers (i.e. corner stores, gas-marts, dollar stores and pharmacies). The present study aimed to: (i) describe customer characteristics, shopping frequency and reasons for shopping at small and non-traditional food retailers; and (ii) describe food/beverage purchases and their nutritional quality, including differences across store type. Data were collected through customer intercept interviews. Nutritional quality of food/beverage purchases was analysed; a Healthy Eating Index-2010 (HEI-2010) score for purchases was created by aggregating participant purchases at each store. Small and non-traditional food stores that were not WIC-authorized in Minneapolis and St. Paul, MN, USA. Customers (n 661) from 105 food retailers. Among participants, 29 % shopped at the store at least once daily; an additional 44 % shopped there at least once weekly. Most participants (74 %) cited convenient location as the primary draw to the store. Customers purchased a median of 2262 kJ (540 kcal), which varied by store type (P=0·04). The amount of added sugar far surpassed national dietary recommendations. At dollar stores, participants purchased a median of 5302 kJ (1266 kcal) for a median value of $US 2·89. Sugar-sweetened beverages were the most common purchase. The mean HEI-2010 score across all stores was 36·4. Small and non-traditional food stores contribute to the urban food environment. Given the poor nutritional quality of purchases, findings support the need for interventions that address customer decision making in these stores.


Threshold estimation based on local minima for nucleus and cytoplasm segmentation.
Image segmentation is the process of partitioning an image into separate objects or regions. It is an essential step in image processing to segment the regions of interest for further processing. We propose a method for segmenting the nuclei and cytoplasms from white blood cells (WBCs). Initially, the method computes an initial value based on the minimum and maximum values of the input image. Then, a histogram of the input image is computed and approximated to obtain function values. The method searches for the first local maximum and local minimum from the approximated function values in the order of increasing of knots sequence. We approximate the required threshold from the first local minimum and the computed initial value based on defined conditions. The threshold is applied to the input image to binarize it, and then post-processing is performed to obtain the final segmented nucleus. We segment the whole WBC before segmenting the cytoplasm depending on the complexity of the objects in the image. For WBCs that are well separated from red blood cells (RBCs), n thresholds are generated and then produce n thresholded images. Then, a standard Otsu method is used to binarize the average of the produced images. Morphological operations are applied on the binarized image, and then a single-pixel point from the segmented nucleus is used to segment the WBC. For images in which RBCs touch the WBCs, we segment the whole WBC using SLIC and watershed methods. The cytoplasm is obtained by subtracting the segmented nucleus from the segmented WBC. The method is tested on two different public data sets and the results are compared to the state of art methods. The performance analysis shows that the proposed method segments the nucleus and cytoplasm well. We propose a method for nucleus and cytoplasm segmentation based on the local minima of the approximated function values from the image's histogram. The method has demonstrated its utility in segmenting nuclei, WBCs, and cytoplasm, and the results are satisfactory.


Identification of Clostridium difficile Asymptomatic Carriers in a Tertiary Care Hospital.
The diagnosis of Clostridium difficile infection (CDI) increases concern that asymptomatic carriers of toxigenic C. difficile may be diagnosed with CDI. A matched case control study was conducted in inpatients in a tertiary care center. The first 50 patients with diarrhea and a positive polymerase chain reaction (PCR) test beginning February 1, 2015, were identified as cases. Control patients were hospitalized patients receiving antibiotics, but with no diarrhea, housed in a room as close as possible to each case during the same admission time. A convenience sample of healthcare workers who cared for C. difficile infected patients was also tested. We found two positive PCR results for C. difficile in controls (4.1%). None of these healthcare workers were positive for C. difficile by PCR. There was no difference between groups with respect to overall antibiotic use before the requested PCR for Clostridium difficile (p = 0.359). The majority of cases had a high proportion of gastrointestinal disorders (71.4%) compared with control (8.2%), p < 0.001. Patients with neoplasia had a higher chance of being identified as cases (p = 0.041). PCR should not be the only diagnostic tool but should be complementary to other methods and to the medical history.


Gallbladder absorption increases during early cholesterol gallstone formation.
The hypothesis that the presence of cholelithogenic bile during the early stages of cholesterol gallstone formation promotes gallbladder absorption of water and electrolytes was tested in a prairie dog gallstone model. An increase in gallbladder transport of water and sodium was observed in cholesterol-fed prairie dogs at a time when cholesterol crystals were present, but before gallstone formation. These data suggest that in the presence of cholesterol-saturated bile, in vivo gallbladder absorption is increased during the early stages of cholesterol gallstone formation. The resulting increase in the solute concentration may promote nucleation and, therefore, be an important etiologic factor in cholesterol gallstone formation.


Proliferin, a prolactin/growth hormone-like peptide represses myogenic-specific transcription by the suppression of an essential serum response factor-like DNA-binding activity.
Proliferin (PLF), a protein which has homology to PRL and GH, has been implicated in the regulation of cell growth and differentiation. PLF1 was detected and found to be differentially regulated during myogenesis in the rodent myogenic cell line C2C12. Transient and stable constitutive high level expression of PLF1 repressed expression of the transfected cardiac and skeletal alpha-actin myogenic-specific promoters, but did not affect expression of the cytoskeletal beta-actin and several viral promoters linked to CAT. Stable cotransfection analyses of 5' unidirectionally deleted actin promoters and a PLF expression vector indicated that PLF exerted its effect on transcription down-stream of nucleotide positions -177 and -154 with respect to the start of transcription at 1 in the cardiac and skeletal alpha-actin promoters. Analyses of cells stably transfected with PLF showed reduced levels of MyoD mRNA, a recently identified gene that is sufficient to convert pluripotential 10T1/2 cells into myoblasts. However, transient constitutive expression of MyoD by the Moloney sarcoma virus long terminal repeat did not override the effect of PLF. Electrophoretic mobility shift analysis of nuclear extracts from C2C12 cells stably transfected with a PLF expression vector displayed drastically reduced levels or activity of the CArG-binding factor (CBF) relative to the ubiquitously expressed transcription factor Oct-1. High affinity interaction between CBF and alpha-actin promoter sequences in vitro directly correlates with functional in vivo expression. CBF is a transcription factor that is sufficient and necessary for myogenic-specific transcription, interacts with the promoter sequences targeted by PLF, and is immunologically related to the serum response factor. In conclusion, PLF selectively represses myogenic-specific transcription within the actin multigene family by suppressing the level and/or activity of a trans-acting factor (CBF) that modulates multiple muscle-specific genes. The data provide a molecular explanation for the inhibition of differentiation by an endogenously produced growth factor/hormone that is differentially expressed during myogenesis and a physiologically important antagonistic regulator of muscle-specific transcription.


Exploring feature-based approaches in PET images for predicting cancer treatment outcomes.
Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patient's response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.


[Can we improve influenza vaccination rates in older people with chronic diseases?].
To determine the proportion of older patients (>or= 65 years) with chronic diseases served by the health center studied here who were not vaccinated during the 2001-2002 influenza vaccination campaign, and to find out why they were not vaccinated. Observational, descriptive, retrospective study. The urban health center serving Area 19 in the Community of Valencia (eastern Spain). Of the 29757 inhabitants served by this center (10.4% >or= 65 years), we included 3868 patients registered in chronic disease care programs and 2980 registered in the influenza vaccination program. We found 853 older patients with chronic diseases who were not vaccinated. Vaccination rate for patients with chronic diseases, for older patients, and for older patients with chronic diseases. Audit of the medical records to identify the reasons why some patients in the latter group were not vaccinated. The vaccination rates were 52.12% (95% CI, 50.4-53.9) for older patients, 26.96% (95% CI, 25.6-28.4) for patients with chronic diseases, and 54.43% (95% CI, 51.4-57.5) for older patients with chronic diseases. Of the 853 older patients with chronic diseases who were not vaccinated, 48.17% came to the center at least once during the vaccination campaign, 27.34% had not come to the center since more than 1 year before the campaign, and the cause for nonvaccination was recorded for only 10.4%. Coverage for influenza vaccination in older patients with chronic diseases was low. Intervention to increase vaccination rates is possible in groups of patients for whom accessibility is good.


The BAARA (Biological AutomAted RAdiotracking) system: a new approach in ecological field studies.
Radiotracking is an important and often the only possible method to explore specific habits and the behaviour of animals, but it has proven to be very demanding and time-consuming, especially when frequent positioning of a large group is required. Our aim was to address this issue by making the process partially automated, to mitigate the demands and related costs. This paper presents a novel automated tracking system that consists of a network of automated tracking stations deployed within the target area. Each station reads the signals from telemetry transmitters, estimates the bearing and distance of the tagged animals and records their position. The station is capable of tracking a theoretically unlimited number of transmitters on different frequency channels with the period of 5-15 seconds per single channel. An ordinary transmitter that fits within the supported frequency band might be used with BAARA (Biological AutomAted RAdiotracking); an extra option is the use of a custom-programmable transmitter with configurable operational parameters, such as the precise frequency channel or the transmission parameters. This new approach to a tracking system was tested for its applicability in a series of field and laboratory tests. BAARA has been tested within fieldwork explorations of Rousettus aegyptiacus during field trips to Dakhla oasis in Egypt. The results illustrate the novel perspective which automated radiotracking opens for the study of spatial behaviour, particularly in addressing topics in the domain of population ecology.


His+ reversions caused in Salmonella typhimurium by different types of ionizing radiation.
The yield of his+ reversions in the Ames Salmonella tester strain TA2638 has been determined for 60Co gamma rays, 140 kV X rays, 5.4 keV characteristic X rays, 2.2 MeV protons, 3.1 MeV alpha particles, and 18 MeV/U Fe ions. Inactivation studies were performed with the same radiations. For both mutation and inactivation, the maximum effectiveness per unit absorbed dose was obtained for the characteristic X rays, which have a dose averaged linear energy transfer (LET) of roughly 10 keV/micron. The ratio of the effectiveness of this radiation to gamma rays was 2 for inactivation and about 1.4 for the his+ reversion. For both end points the effectiveness decreases substantially at high LET, i.e., for the alpha particles and the Fe ions. The composition of the bottom and the top agar was the one recommended by Maron and Ames [Mutat. Res. 113, 173-215 (1983)] for application in chemical mutagenicity tests. The experiments with the less penetrating radiations differed from the usual protocol by utilization of a technique of plating the bacteria on the surface of the top agar. As in an earlier study [Roos et al., Radiat. Res. 104, 102-108 (1985)] greatly enhanced yields of mutations, relative to the spontaneous reversion rate, were obtained in these experiments by performing the irradiations 6 h after plating, which differs from the conventional procedure to irradiate the bacteria shortly after plating.


Chronic cerebral hypoperfusion alters the CypA-EMMPRIN-gelatinase pathway: Implications for vascular dementia.
Chronic cerebral hypoperfusion (CCH) is postulated to underlie multiple pathophysiological processes in vascular dementia (VaD), including extracellular matrix dysfunction. While several extracellular matrix proteins, namely cyclophilin A (CypA), extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases (matrix metalloproteinases, MMP-2 and -9) have been investigated in acute stroke, their involvement in CCH and VaD remains unclear. In this study, CypA-EMMPRIN-gelatinase proteins were analysed in a clinical cohort of 36 aged, cognitively unimpaired subjects and 48 VaD patients, as well as in a bilateral carotid artery stenosis mouse model of CCH. Lower CypA and higher EMMPRIN levels were found in both VaD serum and CCH mouse brain. Furthermore, gelatinases were differentially altered in CCH mice and VaD patients, with significant MMP-2 increase in CCH brain and serum, whilst serum MMP-9 was elevated in VaD but reduced in CCH, suggesting complex CypA-EMMPRIN-gelatinase regulatory mechanisms. Interestingly, subjects with cortical infarcts had higher serum MMP-2, while white matter hyperintensities, cortical infarcts and lacunes were associated with higher serum MMP-9. Taken together, our data indicate that perturbations of CypA-EMMPRIN signalling may be associated with gelatinase-mediated vascular sequelae, highlighting the potential utility of the CypA-EMMPRIN-gelatinase pathway as clinical biomarkers and therapeutic targets in VaD.


Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the entorhinal cortex in the macaque monkey.
We used the anterograde tracers Phaseolus vulgaris-leucoagglutinin (PHA-L) and biotinylated dextran amine (BDA) to examine the projections from the lateral, basal, and accessory basal nuclei of the amygdaloid complex to the entorhinal cortex in Macaca fascicularis monkeys. The heaviest amygdaloid projections originate in the lateral nucleus, which innervates the rostrally situated entorhinal fields but does not project to the caudal entorhinal cortex. The most extensive projections originate in the ventral division of the lateral nucleus. Injections in this subdivision lead to moderate to heavy fiber and terminal labeling in the entorhinal cortex, rostral levels of the rostral intermediate El (ER) and lateral fields, (ELr), and light labeling in the olfactory field EO. The projections from all portions of the lateral nucleus terminate most heavily in layer III. Layer II of EO and ER also receives a substantial input from the ventral division of the lateral nucleus. Layer II of ELr receives light innervation from all portions of the lateral nucleus that project to layer III. Projections from the basal nucleus arise mainly from the parvicellular division and are light to moderate in density. Fibers terminate predominantly in ELr, ER, EO, and the caudal portion of the lateral field (Elc); only the most rostral portion of El receives projections. While fibers from the basal nucleus innervate the same layers as the projections from the lateral nucleus, they tend to have a more vertical or radial orientation within the entorhinal cortex. Electron microscopic analysis of these fibers and terminals indicates that they overwhelmingly form asymmetrical synapses onto dendrites and dendritic spines. The accessory basal nucleus provides a light projection to the same regions of the entorhinal cortex innervated by the lateral and basal nuclei.


[Radiolabeling of a new agent for the study of colorectal tumors].
A new Monoclonal Antibody (AcMo) ior-C5, highly specific for the most part of colorectal adenocarcinomas has been developed. The AcMo was labeled with 99mTc by the Schwarz's direct method using molar ratios MAb: reductant of 1:1,000 and 1:2,000. The first molar ratio was the most adequate for the preparation of the radiopharmaceutical. A labeling yield greater than 95% was obtained. Several <<in vitro>> assays were carried out in order to evaluate the stability of the preparation, whose results reflected the presence of the stable complex 99mTc-IgG. The biodistribution patterns for both preparations were similar. The excreting organs behaved like normal. Nevertheless, a greater renal excretion was observed for the preparation of the molar ratio of 1:2.000, which could be due to the presence of low affinity sites observed in this preparation. They are vulnerable to the trans-chelation of the 99mTc toward cysteine or glutathione present in plasma and tissues.


Medication compliance: the patient's perspective.
There has been increasing interest in using outcomes-based research to evaluate quality of care. Compliance with prescribed regimens is an intermediate outcome measure that presumes that a positive health outcome will follow, which is why clinicians and researchers are interested in compliance. Patients, however, use a variety of criteria to determine the value of medication. They may place equal or greater value on personal and often competing nonclinical outcomes. A small but growing literature explores the influence of physical, economic, psychological, and social factors that influence medication use behavior. This literature supports the notion that patients evaluate medication based not only on its clinical effectiveness, but also how it affects all aspects of their lives. Outcomes research on compliance with prescribed medicine should recognize the outcomes valued from the patient's perspective.


Electric field-assisted laser ablation fabrication and assembly of zinc oxide/carbon nanocomposites into hierarchical structures for supercapacitor electrodes.
One of the major challenges in the field of electrochemical energy storage device performance improvement is the development of suitable synthetic materials for electrodes that can provide high power and high energy density features combined with their long-term stability. Here, we have developed a novel two-step approach based on DC glow discharge plasma pre-treatment of a carbon cloth substrate followed by electric field-assisted laser ablation for the synthesis of ZnO/C nanocomposites in a liquid and their simultaneous assembly into hierarchically organized nanostructures onto the pre-processed carbon cloth to produce a supercapacitor electrode. To form such nanostructures, a processed carbon cloth was included in the electrical circuit as a cathode during laser ablation of zinc in water, while a zinc target served as an anode. A series of studies have been performed to explore the structure, morphology, composition and electrochemical characteristics of the synthesized ZnO/C nanocomposites. Application of the external field provided additional possibilities for tuning the particle morphology. The parameters of the obtained nanostructures were shown to depend on the direction of the applied electric field and liquid composition. SEM studies revealed a nanoflower-like morphology of the prepared nanomaterial having potential in supercapacitor applications due to a large surface area. The ZnO/C nanoflowers, deposited onto a carbon cloth substrate, were tested for energy storage by cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) analysis. The results showed a pseudocapacitor behavior with a maximum specific capacitance of about 3045 F g-1 (at a scan rate of 1 mV s-1). These results demonstrate a promising storage efficiency of the synthesized ZnO/C nanocomposite as a material for supercapacitors.


Therapy for nosocomial pneumonia.
Because of a lack of clinical trials, the American Thoracic Society published a consensus statement on nosocomial pneumonia that included recommendations for antibiotic therapy. Almost concurrently, a multicenter study of the need to modify antibiotic therapy in ventilator-associated pneumonia (VAP) and a report specifically studying Pseudomonas VAP independently demonstrated both the appropriateness and some of the inadequacies of the therapies recommended by the American Thoracic Society. Anaerobic involvement as a copathogen was documented in early-onset VAP but probably impacts antibiotic choices little because of the presence of aerobic pathogens. Potential improvements in aminoglycoside treatment were suggested by meta-analysis of once-daily dosing and aerosolization. The most provocative study used decision-analysis techniques to suggest that antibiotic therapy based on clinical diagnosis of VAP would result in greater mortality than withholding antibiotics. Diagnosis of VAP by bronchoscopic and nonbronchoscopic quantitative cultures resulted in improved outcome with antibiotic treatment, possibly the result of documentation of inappropriate empiric antibodies in approximately 40% of cases of late-onset VAP.


Prevalence of spina bifida at birth--United States, 1983-1990: a comparison of two surveillance systems.
Spina bifida is a birth defect of the spinal column that is a substantial contributor to serious developmental disabilities in the United States. The risk for spina bifida and other neural tube defects (NTDs) can be reduced if women consume 0.4 mg of folic acid before and during the first trimester of pregnancy. Public health programs are being developed to prevent many NTDs by increasing the consumption of folic acid by women of childbearing age. To assess the national impact of these programs on the prevalence of NTDs at birth, multistate surveillance is needed to monitor secular trends in birth-prevalence rates. This report summarizes a collaborative effort by CDC and state birth defect surveillance programs in 16 states to a) obtain multistate, population-based data concerning the birth prevalence and descriptive epidemiology of spina bifida and b) determine the usefulness of combining state surveillance data to monitor national trends in the birth prevalence of NTDs. This report presents data from birth defects surveillance systems in 16 states for the period 1983-1990 (specific periods covered varied by state). These findings are compared with CDC's Birth Defects Monitoring Program (BDMP) for the same period. Population-based data about live-born and stillborn infants who have spina bifida were analyzed from 16 state programs. These 16 programs differed in size and racial/ethnic composition of the populations, surveillance methods, and completeness of case ascertainment. Hospital-based data about live-born and stillborn infants who have spina bifida also were analyzed from BDMP, a passive case ascertainment surveillance system that obtains data from participating hospitals in 50 states. From 1983 through 1990, the birth-prevalence rate for spina bifida for the 16 states was 4.6 cases per 10,000 births; the BDMP rate was nearly identical (4.4 cases). State-specific rates varied substantially, ranging from 3.0 (Washington) to 7.8 (Arkansas). Both state-based and BDMP rates varied among racial/ethnic groups; in both systems, the rates were highest for Hispanics and lowest for Asians/Pacific Islanders. In both the state-based surveillance systems and BDMP, the annual rate of spina bifida for the total population declined during the period 1983-1990. Much of this decline can be attributed to increased prenatal diagnosis in the 1980s. However, because of decline in the rates of spina bifida and other NTDs in the United States began before the widespread availability of prenatal diagnostic services, an environmental component may have contributed substantially to the etiologies of these defects. The birth-prevalence rate of spina bifida was slightly higher among females than males. The ratio of female-to-male prevalence rates was 1.2 for both the state-based surveillance systems and BDMP. This ratio varied considerably among racial/ethnic groups and among states. The similarities of rates and trends in the birth prevalence of spina bifida between the state-based surveillance data and the BDMP data indicate that both types of surveillance systems can provide reliable information concerning national trends in the birth prevalence of spina bifida. CDC and state birth defects surveillance programs will use results from this analysis to monitor national trends in the birth prevalence of spina bifida in the United States. Aggregated state-based surveillance data about spina bifida, anencephaly, and other NTDs will facilitate the monitoring of changes in NTDs after implementation of programs to increase folic acid consumption by women of childbearing age.


Antimicrobial Effect of Leaves of Phyllanthus niruri and Solanum nigrum on Caries Causing Bacteria: An In vitro Study.
Solanum nigrum and Phyllanthus niruri are common herbs which are indigeneous to India. Solanum nigrum commonly called 'manathakkali Keerai' in Tamil, forms an indispensable part of South Indian diet. Phyllanthus niruri (keezhanelli in Tamil) is a widely used medicinal plant, the leaves of which have been used extensively in Ayurveda and native medicine to cure various liver ailments. The herbs Solanumnigrum and Phyllanthus niruri have been found to be effective against numerous enteropathogens in various in vitro studies. To assess and compare the antibacterial efficacy of the crude alcoholic extract of the leaves of Solanum nigrum and Phyllanthus niruri against five cariogenic organisms. Standard strains of the micro-organisms were obtained from ATCC (American Type Culture Collection) and MTCC (Microbial Type Culture Collection) which comprised of Streptococcus mutans MTCC no. 890, Streptococcus oralis MTCC no 2696, Lactobacillus acidophillus MTCC no. 10307, Streptococcus sanguis ATCC no. 10556 and Streptococcus salivarius ATCC no. 13419. The organisms obtained were revived and lawn cultured on Trypticase Soy Agar-Blood Agar (TSA-BA) and de Man, Rogosa and Sharpe (MRS) agar media. The antibacterial effect of the dried and powdered leaves of Solanum nigrum and Phyllanthus niruri was tested using agar well diffusion method. The zones of inhibition obtained after incubation were measured and tabulated. The antibacterial activity for the two herbs was compared using the Mann-Whitney test. The antibacterial zones of inhibition obtained for the herb Solanum nigrum was in the range of 12.3-14.6 mm and ranged from 9.7-11.6 mm for the herb Phyllanthus niruri. When the zones of inhibition were compared for the herbs, Solanum nigrum showed significantly greater zones of inhibition compared to Phyllanthus niruri for the organisms Streptococcussanguis, Streptococcus salivarius, Streptococcus oralis and Streptococcus mutans (p-value<0.05). The alcoholic extract of leaves of Solanum nigrum and Phyllanthus niruri showed significant antibacterial activity against cariogenic organisms, with Solanum nigrum being more anti-cariogenic than Phyllanthus niruri.


Regulation of concentrations of mRNA for amylase, trypsinogen I and chymotrypsinogen B in rat pancreas by secretagogues.
Regulation of pancreatic gene expression by the secretory stimulants cholecystokinin-pancreozymin, caerulein and pilocarpine was studied in the rat, by using cloned cDNA probes to quantify concentrations of specific mRNAs (amylase, trypsinogen I and chymotrypsinogen B). It is concluded that long-term pancreatic stimulation results in pre-translational regulation of secretory-protein gene expression, with a preferential accumulation of RNA transcripts encoding serine proteinases, compared with that for amylase.


Developing nursing ethical competences online versus in the traditional classroom.
The development of society and science, especially medical science, gives rise to new moral and ethical challenges in healthcare. In order to respond to the contemporary challenges that require autonomous decision-making in different work contexts, a pedagogical experiment was conducted to identify the readiness and responsiveness of current organisation of nursing higher education in Slovenia. It compared the successfulness of active learning methods online (experimental group) and in the traditional classroom (control group) and their impact on the ethical competences of nursing students. The hypothesis set in the experiment, hypothesis 1 (the experimental group will be successful and will have good achievements in comprehension and application of ethical principles) was confirmed based on pre-tests and post-tests. The hypothesis tested by the questionnaire, hypothesis 2 (according to the students, the active learning methods online in the experimental group have a positive impact on the development of ethical competences) was confirmed. The pedagogical experiment was supported by a multiple-case study that enabled the in-depth analysis of the students' attitudes towards the active learning methods in both settings. The study included Slovenian first-year nursing students (N = 211) of all the enrolled students (N = 225) at the University of Ljubljana and University of Primorska in the academic year 2010/2011. Before the study ethical permission was obtained from the managements of both participating faculties. The students were given all the necessary information of the experiment before the tutorials. No significant difference was found between the two learning settings and both had a positive impact upon learning. The results of the content analysis show that the students' active engagement with the active learning methods in the group enables the development of ethical competences and the related communicative competences, interpersonal skills, collaboration and critical thinking. Active learning methods in the settings compared, online and the traditional classroom, enabled the development of a higher level of knowledge defined by the ability of critical thinking and reflective response, the core of ethical competences. Students develop ethical competence through active engagement in a group work, role play and discussion, and there is no difference between online or traditional learning settings. In the healthcare, it is crucial for providers to be capable of making autonomous decisions and managing various communication situations and contexts in which the moral attitudes and ethical sensibility are essential.


Moderators of the association between brain activation and farsighted choice.
There is equivocal support for the hypothesis that preference for later larger (LL) over sooner smaller (SS) monetary alternatives (e.g., $50 in four months over $30 today) is associated with functioning of the insula and the prefrontal cortex (especially the lateral PFC). In the present study, we re-examined overall neural correlates of choice using a procedure to minimize potential confounds between choice (which is necessarily not under experimental control) and valuation. In addition, we assessed whether choice-related brain activity is moderated by 1) overall level of delay discounting and 2) the degree of stochasticity in individuals' intertemporal choices. Twenty-one participants completed an individualized intertemporal choice task while brain activity was measured using functional Magnetic Resonance Imaging (fMRI). Across participants, LL choice was associated with activity in left dorsolateral prefrontal cortex (dlPFC), left insula/inferior frontal gyrus (IFG), frontal pole and the anterior cingulate cortex (ACC). Stochasticity positively moderated the LL>SS activity within the left insula and left IFG. Degree of discounting also interacted with choice related activity, but only outside the LL vs. SS main effect map (in the posterior cingulate cortex, and precentral/postcentral gyrus and left dlPFC). Main effect results are consistent with the notion that lateral prefrontal activity during intertemporal decisions bias selection in the direction of LL. Correlation findings indicate that choice related activity in the left insula and IFG is moderated by the stochasticity of intertemporal choices, and may reflect reduced "executive function" demands among highly consistent participants.


Impaired left ventricular energy metabolism in patients with hypertrophic cardiomyopathy is related to the extension of fibrosis at delayed gadolinium-enhanced magnetic resonance imaging.
Areas of intramyocardial late enhancement (LE) at delayed enhanced magnetic resonance imaging (DE-MRI) and reduction of myocardial phosphocreatine (PCr)/ATP-ratio at phosphorus magnetic resonance spectroscopy ((31)P-MRS) are both reported in hypertrophic cardiomyopathy (HCM) and indicate areas of increased interstitial myocardial space with fibrosis and impairment of myocardial energy metabolism, respectively. We sought to ascertain whether in HCM patients the abnormal features of left ventricular (LV) interstitial space revealed by DE-MRI correlated with impaired LV energy metabolism shown at (31)P-MRS. 19 patients with HCM proved by histological analysis of multiple endomyocardial biopsies and with normal coronary arteries, underwent cardiac MRI including DE-MRI and (31)P-MRS. DE-MRI for detection and quantification of late enhancement (LE) and (31)P-MRS to assess the myocardial PCr/ATP-ratio were performed by means of a 1.5-T magnet. 19 healthy subjects, matched for gender and age were studied by (31)P-MRS as control group. LE areas in the LV wall were found in 17 out of 19 patients with an extension ranging from 0.8% to 19.5% of the LV-mass (mean value 7.6% (SD 5.6%). The PCr/ATP-ratio was lower in HCM patients than in control subjects (2.18 (0.41) vs 2.41 (0.30); p<0.05). LE% and PCr/ATP-ratio were inversely related (R = -0.57; p<0.05) and LE% was the stronger predictor of PCr/ATP-ratio by multivariate analysis. This study demonstrated that the known alteration of the PCr/ATP-ratio observed in HCM patients is correlated with the presence of fibrotic areas in the myocardium of the left ventricle.


[Craniosynostosis operations in childhood].
Premature osteosynthesis of one or more cranial bones, either intrauterine or within the first postnatal months, is defined as craniosynostosis. The resulting limitation of intracranial space can cause retardation of cranial growth which, in turn, leads to craniostenosis with increasing intracerebral pressure. Complex forms of craniosynostosis with concomitant malformations (i.e. Apert-, Crouzon-, and Pfeiffer syndromes) must be principally distinguished from simple craniosynostosis. This complex cranio-facial dysostosis is a premature osteosynthesis of cranial and facial bones. In general, as far as Germany is concerned, the incidence of cranio-synostosis amounts to 1/1000 births. If they remain untreated, many of these children will suffer from cortex-associated retardation of intelligence. Surgical management, therefore, is initiated at a very early stage, and should be performed in specialised centres. Recommendations for operation vary from an age of 4 to 36 months. However, an age of 6 months or more is the most frequently preferred age for surgical intervention. Severe respiratory disorders, as well as impossibility of enteral intake of nourishment, are considered absolute indications for surgery, independent of the age; elimination of the stigmatisation regarding environmental contacts of the child is another mandatory indication for operation. The goal of early surgery is reconstruction of physiological, cranial, and facial bone structures ("fronto-orbital" or "fronto-facial advancement"). Correction of craniofacial malformation may be associated with--in part--severe complications for the child. From the anaesthesiologist's point of view, this disease demands highly qualified perioperative management, since a variety of idiosyncrasies and risks must be taken into account: These are, for example, venous air embolism, hypothermia, disorders of water and electrolyte equilibrium, and, extremely vital, difficult intubation and substantial blood loss.


Clinical and economic burden of Richter syndrome in inpatient cases of chronic lymphocytic leukemia within the United States, 2001-2010.
Richter syndrome (RS) is an aggressive transformation of chronic lymphocytic leukemia (CLL) characterized by poor prognoses. The purpose of this study was to assess clinical and economic characteristics of RS within inpatient hospital settings in the United States from 2001 to 2010. This retrospective cohort study employed data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. Overall, 46 613 cases of RS were observed across 695 080 inpatient cases of CLL, representing a national bill of $2.74 billion and involving a 9.3% inpatient mortality rate. Multivariate analyses found decreased national inpatient mortality from 2001 to 2010 of - 61.1% (p < 0.001), shorter length of stay of - 15.5% (p < 0.001) and higher charges of +20.9% (p = 0.003). Numerous characteristics were also associated with increased likelihoods of death, lengths of stay and charges. Clinically, the findings allow for an increased understanding of population-based RS case-mixes, outcome prediction and clinical risk assessments. The continued burden of illness of either RS or CLL ultimately remains contingent upon the comparative- and cost-effectiveness of both existing interventions and those in development.


Does arterio-venous fistula creation affects development of pulmonary hypertension in hemodialysis patients?
Pulmonary arterial hypertension (PAH) is a common complication in hemodialysis (HD) patients and its pathogenesis is not explained clearly. Arterio-venous fistulas (AVFs) creation may contribute to the development of PAH because of increased pulmonary artery blood flow. However, it was not prospectively evaluated that effect of AVF on the development of PAH. We aimed to evaluate the effects of AVF on PAH and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in HD patients. The prospective study included 50 patients with end-stage renal disease. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in the patients. After mean 76.14 ± 11.37 days, the second evaluation was performed by echocardiography. Before AVF creation, 17 (34%) out of 50 patients had PAH. The systolic PAP was significantly higher in the patients with PAH compared with patients without PAH (47.82 ± 9.82 mmHg vs. 30.15 ± 5.70 mmHg, respectively, p = 0.001). In the second evaluation, 19 (38%) out of 50 patients had PAH. The systolic PAP values were significantly higher in the patients with PAH compared with patients without PAH (47.63 ± 8.92 mmHg vs. 25.03 ± 7.69 mmHg, P = 0.001, respectively). There was no relationship between the blood flow rate of AVF and PAP. PAH is a common problem in HD patients. AVF has no significant effect on the development of PAH within a short period. Similarly, blood flow rate of AVF also did not affect remarkably the systolic PAP.


The role of employers and supervisors in promoting pesticide safety behavior among Florida farmworkers.
Farmworkers in Florida's nursery and fernery industries have an elevated risk of exposure to chemical pesticides due to the enclosed nature of their workplaces and their close contact with pesticide-treated plant material. Farmworkers' beliefs about chemical exposures and their perception of employer's or supervisor's valuing of safety may limit the practice of workplace hygiene. Three hundred eighty-two surveys from workers in the nursery and fernery industries in North Central Florida were collected as part of the Together for Agricultural Safety (TAS) Project from 1999-2001. Univariate analyses and multivariate Ordinary Least Squares regression are used to examine the role of individual and structural characteristics on handwashing practices. Workplace practices such as the provision of written notices of recent pesticide application and the provision of convenient handwashing facilities are important predictors of workplace hygiene. Although farmworker attitudes and beliefs towards the utility of such practices and potential hazards are associated with behavior, they are less significant than the structural variables. In order for farmworkers to engage in safety behavior that will protect their health, they must be adequately instructed and supported by employers and/or supervisors.


Mixed-Methods Evaluation of Father Participation in an Adolescent Obesity Prevention Program With Multiple Delivery Methods.
Padres Preparados, Jóvenes Saludables was a Latino family-based obesity prevention intervention implemented from 2017 to 2020 across eight programs in-person only, in a blended format (online/in-person), and online only. The intervention aimed to enhance father parenting skills to improve adolescent diet and activity behaviors. Mothers were encouraged to attend. Factors associated with participation were explored using a mixed-methods, qualitative (focus group/individual interviews by Zoom) and quantitative (process evaluation) design. Eleven focus group and 24 individual interviews were completed after participation with 24 fathers, 27 mothers, and 40 adolescents with responses not sorted by delivery method before analysis. Binomial logistic regression models examined associations between fathers' program completion and predictor variables of delivery characteristics, father demographic characteristics, and family attendance patterns. Parents were married (96% fathers, 76% mothers), had low income, a high school education or less (68% fathers, 81% mothers), and had lived in the United States a mean of 19 years. Parents were motivated to participate to improve health, and to be involved with and improve communication with their child. Common barriers to participation were work and life priorities and programmatic factors including scheduling conflicts and technological issues. Participation was greater for fathers attending sessions in-person compared with online only (OR = 11.6). Fathers were more likely to participate if they attended sessions with family members vs. not attending with family members (OR = 7.2). To maximize participation, findings suggest involving multiple parents/caregivers and adolescents, addressing contextual and programmatic barriers, and promoting benefits of better health and relations with family members.


Adrenocortical activity and the Brazelton Neonatal Assessment Scale: moderating effects of the newborn's biomedical status.
The Brazelton Neonatal Behavioral Assessment Scale with Kansas Supplement (NBAS-K) was administered midway between feedings to 60 newborns who were between 32 and 122 hours old. 35 of the newborns were classified as extremely healthy and normal (Subgroup I), whereas 25 (Subgroup II) were characterized by slight perinatal problems including gestational age 36-37 weeks or 42+ weeks, and fetal distress during labor. All of the newborns were healthy enough to be cared for in a healthy newborn, Level I nursery. Immediately following administration of the NBAS-K, a blood sample was obtained for plasma cortisol determination. Correlations between behavioral responding on the NBAS-K and levels of plasma cortisol revealed few significant relations for the sample as a whole. When the 2 subgroups were examined separately, a number of significant relations emerged. Newborns in Subgroup I who were more competent in their motor control and state regulation capacities as assessed by Lester's Cluster Scores for the NBAS-K exhibited higher levels of plasma cortisol. In contrast, newborns in Subgroup II who exhibited a greater adrenocortical response to the examination showed more behaviors indicative of high behavioral arousal and distress. This pattern of relations for Subgroup II appeared to be mediated by the number of hours that had elapsed since delivery. As postpartum time increased, the strength of the association between adrenocortical activity and behavioral arousal/distress decreased for Subgroup II. A systems theory approach is used to interpret the difference in patterns of correlations found for the 2 subgroups.


Histiocytic Sarcoma with p16-Overexpression Presenting as Uterine Cervical Mass.
A 67-year-old woman presented with post-menopausal bleeding. Physical examination and imaging revealed a cervical mass with extensive pelvic involvement and supraclavicular lymphadenopathy. Clinical diagnosis was stage IVB cervical carcinoma. Cervical biopsy revealed high-grade squamous intraepithelial lesion and epithelioid tumor cells in the stroma. Lymph node biopsy revealed metastasis by similar epithelioid tumor cells. The epithelioid tumor cells were positive for p16, CD68, and CD163 on immunohistochemical study. The diagnosis of histiocytic sarcoma (HS) was rendered. This case demonstrated a rare presentation of HS mimicking cervical carcinoma. Awareness of this rare entity with appropriate ancillary tests is essential for accurate diagnosis. In contrast to the previous postulation of p16-inactivation as the pathogenesis of HS, p16-overexpression might suggest a different pathway for tumorigenesis.


Physical activity and the risk of colorectal adenomas.
Physical activity has repeatedly been shown to protect against colorectal cancer. Since adenomas are precursors to most colorectal cancers, we examined the relation of physical activity to the risk for colorectal adenomas in a colonoscopy-based study of 200 adenoma cases and 384 adenoma-free controls. Physical activity was assessed by telephone using a modification of a validated questionnaire comprising 17 items concerning three activity dimensions: leisure, work, and sport. Dietary information was obtained with a validated semiquantitative food frequency questionnaire. We created indices for each dimension of physical activity, which we categorized by quartile. Using logistic regression analysis, we found that leisure activity protected women against colorectal adenomas. Women in the second through fourth quartiles were considerably less likely than those in the first quartile to develop adenomas [crude odds ratio = 0.48; 95% confidence interval (CI) = 0.28-0.81]. There was no protective effect of work activity among either men or women. Men who participated in no sport were at increased risk for adenomas (odds ratio = 1.68; 95% CI = 0.93-3.02). Physical activity appears to protect against both colorectal cancer and colorectal adenomas.


Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice.
The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults. We performed an in vivo study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant. We measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and genome-wide chromatin accessibility in lung tissue from two genetically divergent inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice exposed to a model DNA-damaging chemical, 1,3-butadiene. Our results showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage, we observed increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon chemical exposure, chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that acquired higher levels of 1,3-butadiene-induced DNA damage, around the same genes, ultimately resembling the molecular profile of CAST/EiJ. These results suggest that strain-specific changes in chromatin and transcription in response to chemical exposure lead to a "compensation" for underlying genetic-driven interindividual differences in the baseline chromatin and transcriptional state. This work represents an example of how chemical and environmental exposures can be evaluated to better understand gene-by-environment interactions, and it demonstrates the important role of chromatin response in transcriptomic changes and, potentially, in deleterious effects of exposure. https://doi.org/10.1289/EHP1937.


Quadrennial review of a paediatric emergency assessment unit.
The primary aim of this article is to report on one aspect of a quadrennial study designed to explore the appropriateness and impact of the development of a paediatric emergency assessment unit (PEAU) as a response to increases in paediatric emergencies presenting to a south-western regional child health unit. In particular, this article will present the findings of a prospective audit of admissions to the PEAU over a 1-month period during the latter part of 2002. The primary method of data collection utilized a structured survey instrument developed using a design and automatic data computer software package, completed by the nursing staff. Anonymized descriptive data were obtained from 223 children admitted to the PEAU during one calendar moth and authorized by the appropriate clinical directorate audit committee as part of its ongoing commitment to the full implementation of clinical governance. The data presented primarily relate to children admitted during the official opening times of the PEAU, and those presenting out of hours. The data analysis demonstrates a reduction in the number of children staying overnight in hospital since the opening of the PEAU, with the majority of children being referred by their own family doctor. Only one child in the sample was readmitted to the PEAU within 24 hours, and two within 24 hours of discharge as inpatients. Although thought to be pertinent, only one child admitted after official closing of the PEAU and out of hours was described as being admitted for social reasons. The International Classification of Diagnosis (ICD) 10 (World Health Organization (WHO), 1994) classifications of the children admitted to the PEAU reflect those found in other similar studies. Overall, the results of this investigation demonstrate that a PEAU can offer an efficient service to GPs, families and others as a route of referral, thus mitigating unnecessary overnight stays for individual children.


Intrarenal activation of endothelin type B receptors improves kidney oxygenation in type 1 diabetic rats.
About one-third of patients with type 1 diabetes develops kidney disease. The mechanism is largely unknown, but intrarenal hypoxia has been proposed as a unifying mechanism for chronic kidney disease, including diabetic nephropathy. The endothelin system has recently been demonstrated to regulate oxygen availability in the diabetic kidney via a pathway involving endothelin type A receptors (ETA-R). These receptors mainly mediate vasoconstriction and tubular sodium retention, and inhibition of ETA-R improves intrarenal oxygenation in the diabetic kidney. Endothelin type B receptors (ETB-R) can induce vasodilation of the renal vasculature and also regulate tubular sodium handling. However, the role of ETB-R in kidney oxygen homeostasis is unknown. The effects of acute intrarenal ETB-R activation (sarafotoxin 6c for 30-40 min; 0.78 pmol/h directly into the renal artery) on kidney function and oxygen metabolism were investigated in normoglycemic controls and insulinopenic male Sprague-Dawley rats administered streptozotocin (55 mg/kg) 2 wk before the acute experiments. Intrarenal activation of ETB-R improved oxygenation in the hypoxic diabetic kidney. However, the effects on diabetes-induced increased kidney oxygen consumption could not explain the improved oxygenation. Rather, the improved kidney oxygenation was due to hemodynamic effects increasing oxygen delivery without increasing glomerular filtration or tubular sodium load. In conclusion, increased ETB-R signaling in the diabetic kidney improves intrarenal tissue oxygenation due to increased oxygen delivery secondary to increased renal blood flow.


Fetal Alcohol Spectrum Disorders in a Rocky Mountain Region City: Child Characteristics, Maternal Risk Traits, and Prevalence.
To document prevalence and traits of children with fetal alcohol spectrum disorders (FASD) and maternal risk factors in a Rocky Mountain city. Variations on active case ascertainment methods were used in 2 first-grade cohorts in all city schools. The consent rate was 59.2%. Children were assessed for physical growth, dysmorphology, and neurobehavior and their mothers interviewed. Thirty-eight children were diagnosed with FASD and compared with 278 typically developing controls. Total dysmorphology scores summarized well the key physical indicators of FASD and defined specific diagnostic groups. On average, children with FASD performed significantly poorer than controls on intellectual, adaptive, learning, attention, and behavioral tasks. More mothers of children with FASD reported drinking prior to pregnancy and in the first and second trimesters, and had partners with drinking problems than mothers of controls; however, reports of comorbid alcohol use and 6 other drugs were similar for mothers of children with FASD and mothers of controls. Mothers of children with FASD were significantly younger at pregnancy, had lower average weight before pregnancy and less education, initiated prenatal clinic visits later, and reported more health problems (e.g., stomach ulcers and accidents). Children with FASD had significantly lower birth weight and more problems at birth, and were less likely to be living with biological mother and father. Controlling for other drug and tobacco use, a FASD diagnosis is 6.7 times (OR = 6.720, 95% CI = 1.6 to 28.0) more likely among children of women reporting prepregnancy drinking of 3 drinks per drinking day (DDD) and 7.6 times (OR = 7.590, 95% CI = 2.0 to 31.5) more likely at 5 DDD. Prevalence of FAS was 2.9-5.8 per 1,000 children, and total FASD was 34.9 to 82.5 per 1,000 children or 3.5 to 8.3% at this site. This site had the second highest prevalence of FASD of the 4 Collaboration on FASD Prevalence sites and clearly identifiable child and maternal risk traits.