Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (op/op) mice after macrophage depletion.
We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1) played important roles in the process of the repopulation of Kupffer cells after their elimination by administration of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP). In this study, we examined the repopulation of Kupffer cells and splenic red pulp macrophages in osteopetrotic (op/op) mice defective in the production of functional M-CSF and their littermate mice by using the lipo-MDP model. In untreated op/op mice, numbers of F4/80-positive Kupffer cells in the liver and F4/80-positive splenic red pulp macrophages were reduced. Repopulation of Kupffer cells and splenic macrophages was observed in littermate (op/+) mice liver by 14 days after depletion. However, in op/op mice, repopulation of Kupffer cells was not observed in Kupffer-cell-depleted op/op mice until 56 days after depletion, whereas splenic red pulp macrophages repopulated and recovered to the level of control op/op mice by 10 days after depletion. Single injection of M-CSF was effective for the induction of the repopulation of Kupffer cells, and daily administration of M-CSF induced remarkable repopulation and maturation of Kupffer cells and proliferation of macrophage precursor cells in the liver of Kupffer-cell-depleted op/op mice. These results suggest that Kupffer cells are completely M-CSF-dependent tissue macrophages, whereas splenic red pulp macrophages are composed of M-CSF-dependent macrophages and M-CSF-independent macrophages. This mouse model provides a useful tool for the study of effects of growth factor on Kupffer cell differentiation in vivo.


The importance of measuring the velocity of diameter expansion on MRI in upfront management of suspected WHO grade II glioma - case report.
A right insular lesion was incidentally discovered in a 48-year-old male. Morphological and metabolic radiological characteristics on magnetic resonance imaging (MRI) were in favor of a World Health Organization (WHO) grade II glioma. Despite being advised that surgery was appropriate, the patient elected for conservative management. A second MRI was performed 5 months after, and interpreted as unchanged. A third MRI 4 months later demonstrated a significant increase in tumor size and enhancement in a new distant tumor focus. The patient was referred to our center and underwent surgical resection. Histopathology revealed a grade III astrocytoma. A retrospective quantitative measurement of the radiological growth between the two first MRIs yielded a growth rate of 12 mm/year. This value, highly suggestive of a malignant glioma, should have triggered surgery at the time of the second MRI. We conclude that, whenever surgical treatment of a suspected WHO grade II gliomas is postponed, assessing tumor kinetics quantitatively is important to identify patients whose tumor is indeed a WHO grade III glioma. The tumor should be indeed followed by serial MRIs with quantitative measurement of tumor growth, not just "eyeball" qualitative examination. Immediate treatment is indicated in patients with radiological tumor expansion of greater than 8mm/year.


Enhanced surface functionality and microbial fuel cell performance of chitosan membranes through phosphorylation.
The effects of plasticization and cross-linking on the performance of chitosan as promising proton exchange membranes (PEMs) for bioelectricity generation in microbial fuel cells (MFCs) were investigated. The physico-chemical properties of chitosan (CS), sorbitol-chitosan (S-CS), phosphorylated-chitosan (CS-P) and phosphorylated-sorbitol-chitosan (S-CS-P) membranes were investigated by FESEM-EDS, FTIR-ATR, XRD, TGA, tensile strength and sorption studies. The performance of the fabricated PEMs was assessed by power density and cation exchange capacity (CEC). Maximum power densities achieved were 130.03, 20.76, 94.59 and 7.42mW/m(2) for CS-P, S-CS-P, S-CS and CS membranes respectively. Phosphorylation of the CS membranes increased CEC and tensile strength, attributed to an increase in bonded amide and phosphate ionic surface groups. Further, 49.07% COD removal from municipal wastewater was achieved with CS-P membranes. Thus, through chemical modifications, the physico-chemical and mechanical properties of natural abundant biopolymer chitosan can be enhanced for its use as an environmentally sustainable PEM in MFC technology.


The Effect of EECP on Ischemic Heart Failure: a Systematic Review.
Heart failure is a serious global health problem, and coronary artery disease is one of the main causes. At present, the treatment options for ischemic heart failure (IHF) are limited. This article mainly aims to explore the evidence of enhanced external counterpulsation (EECP) as a non-invasive cardiac rehabilitation method in patients with IHF and to make a preliminary exploration of its mechanisms. According to the existing evidence, the standard course of EECP is safe in patients with IHF and can significantly improve the quality of life of these patients. The effect of EECP on systolic function is still unclear, while EECP has a significant improvement effect on cardiac diastolic function. At the same time, this treatment can reduce the re-hospitalization rate and emergency visit rate of patients within 6 months. In terms of mechanisms, in addition to the immediate hemodynamic effect, existing evidence mostly suggests that its improvement of cardiac function may come from its upregulation of shear stress to improve myocardial perfusion. EECP is safe to use in patients with stable ischemic heart failure, and it can improve the performance status of patients and may be beneficial to cardiac function and reduce the short-term re-hospitalization rate.


Insights into the Establishment of Chromatin States in Pluripotent Cells from Studies of X Inactivation.
Animal development entails the sequential and coordinated specialization of cells. During cell differentiation, transcription factors, cell signaling pathways, and chromatin-associated protein complexes cooperate in regulating the expression of a large number of genes. Here, we review the present understanding of the establishment of chromatin states by focusing on X chromosome inactivation (XCI) as a model for facultative heterochromatin formation in female embryonic cells. The inactive X chromosome is large enough to be investigated by biochemical and microscopy techniques. In addition, the ability to compare the inactivated chromatin to the active X in male cells enables us to differentiate events specific to gene silencing during XCI from gene regulatory effects from changing pathways in the same cell. Findings in XCI are useful as blueprints for investigation of the action of epigenetic pathways in differentiation and lineage commitment. We summarize recent studies that have identified factors that are critical for chromosome-wide gene repression in XCI, and we discuss their implications for epigenetic regulation in pluripotent cells of the early embryo.


Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study).
Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid. SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression). Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%. In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.


Sitagliptin improves functional recovery via GLP-1R-induced anti-apoptosis and facilitation of axonal regeneration after spinal cord injury.
Axon growth and neuronal apoptosis are considered to be crucial therapeutic targets against spinal cord injury (SCI). Growing evidences have reported stimulation of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) signalling axis provides neuroprotection in experimental models of neurodegeneration disease. Endogenous GLP-1 is rapidly degraded by dipeptidyl peptidase-IV (DPP4), resulting in blocking of GLP-1/GLP1R signalling process. Sitagliptin, a highly selective inhibitor of DPP4, has approved to have beneficial effects on diseases in which neurons damaged. However, the roles and the underlying mechanisms of sitagliptin in SCI repairing remain unclear. In this study, we used a rat model of SCI and PC12 cells/primary cortical neurons to explore the mechanism of sitagliptin underlying SCI recovery. We discovered the expression of GLP-1R decreased in the SCI model. Administration of sitagliptin significantly increased GLP-1R protein level, alleviated neuronal apoptosis, enhanced axon regeneration and improved functional recovery following SCI. Nevertheless, treatment with exendin9-39, a GLP-1R inhibitor, remarkably reversed the protective effect of sitagliptin. Additionally, we detected the AMPK/PGC-1α signalling pathway was activated by sitagliptin stimulating GLP-1R. Taken together, sitagliptin may be a potential agent for axon regrowth and locomotor functional repair via GLP-1R-induced AMPK/ PGC-1α signalling pathway after SCI.


The phylogeny of the subgroups within the melanogaster species group: likelihood tests on COI and COII sequences and a Bayesian estimate of phylogeny.
The relationships among the majority of the subgroups in the Drosophila melanogaster species group remain unresolved. We present a 2223basepair dataset for mitochondrial cytochrome oxidase I and cytochrome oxidase II for 43 species (including new data from 11 species), sampled to include the major subgroups. After a brief review of competing hypotheses for the ananassae, montium, suzukii, and takahashii subgroups, we combine the two genes based on a new use of the SH test and present KH and SH likelihood comparisons (Kishino and Hasegawa, 1989. J. Mol. Evol. 29, 170-179; Shimodaira and Hasegawa, 1999) to test the monophyly and placement of these subgroups within the larger species group. Although we find insignificant differences between the two suggested placements for the ananassae subgroup, the ananassae is sister to the rest of the subgroups in the melanogaster species group in every investigation. For the takahashii subgroup, although we cannot reject monophyly, the species are so closely related to the suzukii subgroup for these data that the two subgroups often form one clade. Finally, we present a Bayesian estimate of the phylogeny for both genes combined, utilizing a recently published method that allows for different models of evolution for different sites.


Changes in thyrotroph and somatotroph cell populations induced by stimulation and inhibition of their secretory activity.
The populations of cells which produce immunoreactive growth hormone (GH) and thyroid stimulating hormone (TSH) in the rat pituitary gland do not occur in fixed percentages but vary greatly under different physiological and experimental conditions. These variations can be directly correlated to the levels of stimulation and/or inhibition of the specific secretory activity. In both types of cell, sustained stimulation with trophic hormones or blockage of the feedback mechanisms induces remarkable growth in the specific cell population. Conversely, the interruption or inhibition of the stimulus thwarted the hormonal secretion and caused a massive degeneration of redundant cells. The stimulation of both GH and TSH cells is accompanied by an enhanced secretory activity as judged by their higher concentrations in serum and hypertrophy of the cytoplasmic organelles involved in synthesis and intracellular processing of the hormones. By contrast, interruption of the stimulus is followed by a variable degree of disruption of the cytoplasmic organization, including a sizable degeneration of cells. In stimulated rats, the concentrations of both GH and TSH decreased significantly in pituitary tissue due to mobilization of the hormonal stores contained in secretory granules. On the other hand, the withdrawal of stimuli blocked the hormonal release; this is reflected by the accumulation of both hormones and secretory granules in pituitary tissue. The strict correlation between the size of the GH and TSH populations with stimulation and inhibition of hormonal secretory activity reported in this investigation further supports the critical role played by the cell renewal process in endocrine secretion.


Clinical manifestations of trisomy 4p syndrome.
Trisomy 4p syndrome is a distinct clinical entity which was noted almost a quarter century ago by Wilson et al. [71] and later was delineated by Gonzalez and colleagues [29]. The variation in the length of duplicated segment usually associated with monosomy of other genetic material which has resulted in confusion and as a result a so-called 4p syndrome could not be recognized without cytogenetic analysis. We wish to draw the attention of clinicians to this subject by presenting the description of over 75 cases including one from our clinic and stress the point that molecular approaches are imperative to characterize this anomaly. After extensive review, it appears that patients retaining at least the distal two-thirds to the entire short arm share an overlapping phenotypic expression that constitutes pure trisomy 4p syndrome which includes prominent glabella, bulbous nose with flat or depressed nasal bridge, retrognathia, pointed chin, short neck with low hairline, enlarged ears with abnormal helix and antihelix, rocker-bottom feet with prominent heel. Arachnodactyly and camptodactyly. Molecular characterization of 4p is imperative. We have also included an extensive bibliography for clinicians who may find it useful as a single reference source for evaluating their future cases. The 4p-syndrome is a distinct entity but without cytogenetic evaluation, the syndrome can not be recognized.


A cytogenetic study of 47,XXY males of known origin and their parents.
A number of patients with both sex chromosome aneuploidy and the fragile X syndrome have been reported and this has led to the hypothesis that females heterozygous for the fragile X mutation have an increased rate of meiotic nondisjunction. Furthermore the suggestion has frequently been made that a predisposition to meiotic nondisjunction is associated with an increase in mitotic nondisjunction. We have tested these two hypotheses by examining the chromosomes of a series of 47,XXY males and their parents. In the majority the parental origin of the additional sex chromosome was known. The cells were cultured under conditions suitable for demonstrating the fragile X and 100 cells were scored 'blind' from the patients and both parents. No fragile X individual was seen and there was no difference in the proportion of aneuploid cells between the parents in whom the nondisjunction event occurred and the control parents. Therefore, our results lend no support to the suggestions that the fragile X is associated with an increase in sex chromosome aneuploidy or that individuals in whom meiotic nondisjunction occurs have an increased level of mitotic nondisjunction.


Lifetime impact of being underweight or overweight/obese during childhood in Vietnam.
There is limited evidence about lifetime burden of child malnutrition. This study aimed to estimate the lifetime impact of being underweight or overweight/obese during childhood in Vietnam. We developed a life table model in combination with a Markov model for Vietnamese children aged 5-19 years and simulated until they reached 75 years of age or died using published data. The starting year was 2019 and the model estimated number of deaths, years of life lived and quality-adjusted life years (QALY) with an annual discount rate of 3%. We performed scenario, one-way, and probabilistic sensitivity analyses to assess the impact of uncertainties in input parameters. The model estimated 9.68 million deaths (6.44 million men and 3.24 million women), 622 million years of life lived (317 million men and 305 million women), and 601 million QALYs (308 million men and 293 million women). Scenario analyses showed that the reduction in either underweight or overweight/obesity alone, and reduction in both underweight and overweight/obesity resulted in fewer deaths, more years of life lived and more QALYs gained. In the scenario where everyone was a healthy weight, the model estimated 577,267 fewer deaths (6.0% less), 2 million more years of life lived (0.3% more), and 3 million QALYs gained (0.6% more) over base-case results which represents current situation in Vietnam. Our results suggest that addressing underweight and overweight/obesity will contribute to reducing deaths and increasing years of life lived and QALYs. Policies and interventions in alignment with Sustainable Development Goals to address underweight and overweight/obesity are necessary to achieve health for all.


Phospholipase D activity in nontransformed and transformed fibroblasts.
Rat embryo fibroblasts (REF52 cells) and the simian virus 40 transformed derivative (WT6 Ag6) were employed to characterize phospholipase D (PLD) activity in normal and transformed cells. In cells prelabeled with [3H]myristic acid or [3H]glycerol and treated with 12-O-tetradecanoylphorbol-13-acetate (TPA, 50 ng/ml medium) or vasopressin (VP, 100 ng/ml medium) in the presence of ethanol, the formation of labeled phosphatidylethanol (PEt) was 3- to 5-fold higher in REF52 cells than in the transformed cells. The transphosphatidylation of phosphatidylcholine (PC) to PEt was further examined in cell-free assay systems. Results demonstrated that the formation of PEt in the cell-free assays was dependent on the mode of substrate presentation and the source of the PC. With endogenous membrane-bound substrate, the formation of [3H]myristoyl-PEt was 5-fold higher in homogenates derived from normal cells as compared to transformed cell homogenates. In experiments using exogenous labeled PC isolated from either REF52 or transformed cells as substrate, cell-free PLD activity differed greatly with regard to the source of the PC. The formation of PEt from REF52-derived PC was approx. 4-fold higher as compared to PEt formed with PC derived from the transformed cells, irrespective of enzyme source. The results demonstrate that PLD in intact nontransformed fibroblasts is activatable by TPA and VP to a greater extent than in the transformed counterpart. The results from cell-free assays suggest that PLD activity is more dependent on the type of PC substrate than on the source of the enzyme.


Detection of HPV-16 in cell lines and cervical lavage specimens by a polymerase chain reaction-enzyme immunoassay assay.
A gene amplification method that combines the polymerase chain reaction with detection of amplified DNA in a solution hybridization/enzyme immunoassay (PCR-EIA) was developed for HPV-16 DNA. Samples were amplified with primers for the E7-E1 region of HPV-16. Amplified DNA products were identified and quantitated by hybridization in solution with a biotinylated RNA probe. Labeled DNA/RNA hybrids were measured semiquantitatively in an enzyme immunoassay using solid phase anti-biotin antibody and liquid phase B-d-galactosidase labeled monoclonal antibody against DNA-RNA hybrids. Enzyme bound to the solid phase was quantitated with a fluorogenic substrate. The assay was linear over 2 log10 dilutions of SiHa cells and the detection limit was three copies of HPV-16 genome. The sensitivity of PCR-EIA for detection of PCR amplified products compared favorably with slot and Southern blots using a 32P-labeled RNA probe. The assay was used to assess HPV-16 infection of uterine cervix in women attending a clinic for sexually transmitted diseases. Twenty-one of the 81 specimens (25.9%), obtained by cervicovaginal lavage, were positive for HPV-16 by PCR-EIA. The assay provides a convenient means to objectively measure HPV DNA amplified with PCR.


Estimation of identification limit for a small-type OSL dosimeter on the medical images by measurement of X-ray spectra.
Our aim in this study is to derive an identification limit on a dosimeter for not disturbing a medical image when patients wear a small-type optically stimulated luminescence (OSL) dosimeter on their bodies during X-ray diagnostic imaging. For evaluation of the detection limit based on an analysis of X-ray spectra, we propose a new quantitative identification method. We performed experiments for which we used diagnostic X-ray equipment, a soft-tissue-equivalent phantom (1-20 cm), and a CdTe X-ray spectrometer assuming one pixel of the X-ray imaging detector. Then, with the following two experimental settings, corresponding X-ray spectra were measured with 40-120 kVp and 0.5-1000 mAs at a source-to-detector distance of 100 cm: (1) X-rays penetrating a soft-tissue-equivalent phantom with the OSL dosimeter attached directly on the phantom, and (2) X-rays penetrating only the soft-tissue-equivalent phantom. Next, the energy fluence and errors in the fluence were calculated from the spectra. When the energy fluence with errors concerning these two experimental conditions was estimated to be indistinctive, we defined the condition as the OSL dosimeter not being identified on the X-ray image. Based on our analysis, we determined the identification limit of the dosimeter. We then compared our results with those for the general irradiation conditions used in clinics. We found that the OSL dosimeter could not be identified under the irradiation conditions of abdominal and chest radiography, namely, one can apply the OSL dosimeter to measurement of the exposure dose in the irradiation field of X-rays without disturbing medical images.


Overlooked hematological markers of disease activity in rheumatoid arthritis.
The aim of this study was to investigate the relationship between hematological markers and disease activity in patients with rheumatoid arthritis (RA). The study was designed and performed in the Department of Rheumatology of the Sakarya University Faculty of Medicine. In total, 102 patients with RA were retrospectively enrolled. We used the Disease Activity Score of 28 joints (DAS28) instrument to evaluate disease activity. Laboratory assessments included complete blood cell counts, measurement of erythrocyte sedimentation rate (ESR) and assessment of C-reactive protein (CRP) level. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or metabolic disorder. We found that the neutrophil lymphocyte ratio (NLR) and mean platelet volume (MPV) varied by disease activity status. NLR values correlated positively with the DAS28 scores of RA patients. Especially, higher NLR values (3.92 ± 0.31) were evident in the group exhibiting high-level disease activity, whereas the MPV values were lowest (7.11 ± 0.91 fL) in this group. Additionally, no significant difference was evident between DAS28 scores and platelet distribution width (PDW) values in patients with RA (r = -0.055, P = 0.124). We found that the MPV value may serve as a marker of the absence of acute-phase disease, and the NLR level as a marker of the presence of such disease, in patients with RA. More detailed analysis of disease activity is required to further explain the associations of the markers described above with disease activity.


Modulation of developmental signals by endocytosis: different means and many ends.
Recent advances have highlighted the importance of endocytic processes in regulating the activity and distribution of developmental signals. Classically, signalling is downregulated by endocytosis and subsequent trafficking to lysosomes (e.g. Notch, Hedgehog, Roundabout). However, endocytosis can also have a positive role in signalling. For example, endocytosis of Delta, the ligand of Notch, is needed for activation of the signal. In the case of signalling by Hedgehog, endocytic trafficking segregates an inhibitory receptor (Patched) from the positive effector (Smoothened). Endosomes could also be the site where signalling is activated (e.g. transforming growth factor beta). Finally, endocytosis could power the transport of morphogens along epithelia.


Time required for elimination of Neisseria gonorrhoeae from the urogenital tract in men with symptomatic urethritis: comparison of oral and intramuscular single-dose therapy.
The spread of sexually transmitted diseases (STDs), including gonorrhea, is affected by the duration of infection. Oral antibiotic therapy for gonococcal infection has been shown to be as effective as conventional intramuscular injection with ceftriaxone. Rapid cure would be expected to limit further spread of gonorrhea. However, the speed with which Neisseria gonorrhoeae is eliminated from the urogenital tract has not been evaluated. To determine the time required for elimination of Neisseria gonorrhoeae for the urine, mucosa, and semen in male subjects after treatment with ceftriaxone (250 mg intramuscularly), ciprofloxacin (500 mg by mouth, single dose) or cefixime (400 mg by mouth, single dose.) In 14 subjects, gonococci were eliminated from the urine within 4 hours of therapy and the mucosa within 24 hours after therapy. In 9 additional subjects, gonococci were eliminated from the semen by 24 hours after therapy. These results support the efficacy of single-dose oral therapy for gonorrhea and suggest that earlier follow-up for proof of cure in clinical trials of new antibiotics for gonorrhea may be acceptable. Rapid elimination of gonorrhea reduces the risk for continued transmission of the organism.


[Ventriculomegaly without dysraphic malformations--retrospective analysis fetuses diagnosed in the Department of Gynecology & Obstetrics of the Postgraduate Center of Medical Education in Warsaw, between 1997-2002].
Our objective was to determine if ventriculomegaly not related to the open neural tube defects is associated with other anomalies and aneuploidy. What we should do after such diagnosis. We also analyzed gestational age at the first examination. We retrospectively studied ultrasound reports of the fetuses with this type of ventriculomegaly. We analyzed 71 cases diagnosed between September 1997 and March 2002. Ventriculomegaly was a assumed to be present when atrial width was equal or greater than 10 mm. Antenatal karyotyping was performed in all fetuses. 21 cases were concomitant with other CNS malformations, in 50 cases ventriculomegaly was the only one brain anomaly. The incidence of chromosomal abnormalities was 8.5% and it was strongly related to the presence of multisystem malformations. The median gestational age at diagnosis was 27.6 weeks. Our results suggest that in fetuses with ventriculomegaly not related to the open neural tube defects a detailed ultrasonographic survey and karyotyping should be done. Furthermore, every pregnant woman should undergo ultrasound screening before the 24th gestational week.


Electrical and structural remodeling contribute to atrial fibrillation in type 2 diabetic db/db mice.
Atrial fibrillation (AF) is highly prevalent in diabetes mellitus (DM), yet the basis for this finding is poorly understood. Type 2 DM may be associated with unique patterns of atrial electrical and structural remodeling; however, this has not been investigated in detail. The purpose of this study was to investigate AF susceptibility and atrial electrical and structural remodeling in type 2 diabetic db/db mice. AF susceptibility and atrial function were assessed in male and female db/db mice and age-matched wildtype littermates. Electrophysiological studies were conducted in vivo using intracardiac electrophysiology and programmed stimulation. Atrial electrophysiology was also investigated in isolated atrial preparations using high-resolution optical mapping and in isolated atrial myocytes using patch-clamping. Molecular biology studies were performed using quantitative polymerase chain reaction and western blotting. Atrial fibrosis was assessed using histology. db/db mice were highly susceptible to AF in association with reduced atrial conduction velocity, action potential duration prolongation, and increased heterogeneity in repolarization in left and right atria. In db/db mice, atrial K+ currents, including the transient outward current (Ito) and the ultrarapid delayed rectifier current (IKur), were reduced. The reduction in Ito occurred in association with reductions in Kcnd2 mRNA expression and KV4.2 protein levels. The reduction in IKur was not related to gene or protein expression changes. Interstitial atrial fibrosis was increased in db/db mice. Our study demonstrates that increased susceptibility to AF in db/db mice occurs in association with impaired electrical conduction as well as electrical and structural remodeling of the atria.


Glycosaminoglycan derivatives: promising candidates for the design of functional biomaterials.
Numerous biological processes (tissue formation, remodelling and healing) are strongly influenced by the cellular microenvironment. Glycosaminoglycans (GAGs) are important components of the native extracellular matrix (ECM) able to interact with biological mediator proteins. They can be chemically functionalized and thereby modified in their interaction profiles. Thus, they are promising candidates for functional biomaterials to control healing processes in particular in health-compromised patients. Biophysical studies show that the interaction profiles between mediator proteins and GAGs are strongly influenced by (i) sulphation degree, (ii) sulphation pattern, and (iii) composition and structure of the carbohydrate backbone. Hyaluronan derivatives demonstrate a higher binding strength in their interaction with biological mediators than chondroitin sulphate for a comparable sulphation degree. Furthermore sulphated GAG derivatives alter the interaction profile of mediator proteins with their cell receptors or solute native interaction partners. These results are in line with biological effects on cells relevant for wound healing processes. This is valid for solute GAGs as well as those incorporated in collagen-based artificial ECM (aECMs). Prominent effects are (i) anti-inflammatory, immunomodulatory properties towards macrophages/dendritic cells, (ii) enhanced osteogenic differentiation of human mesenchymal stromal cells, (iii) altered differentiation of fibroblasts to myofibroblasts, (iv) reduced osteoclast activity and (v) improved osseointegration of dental implants in minipigs. The findings of our consortium Transregio 67 contribute to an improved understanding of structure-function relationships of GAG derivatives in their interaction with mediator proteins and cells. This will enable the design of bioinspired, functional biomaterials to selectively control and promote bone and skin regeneration.


The degree of equity and coupling coordination of staff in primary medical and health care institutions in China 2013-2019.
Primary medical and health care facilities are the first lines of defense for the health of population. This study aims to evaluate the current state and trend of equity and coupling coordination degree (CCD) of staff in primary medical and health care institutions (SPMHCI) based on the quantity and living standards of citizens in China 2013-2019. The research findings are expected to serve as a guideline for the allocation of SPMHCI. The data used in this study including the quantity and living standards of citizens, as well as the number of SPMHCI in 31 provincial administrative regions of China, were obtained from the China Statistical Yearbook and the China Health Statistics Yearbook. The equity and CCD for SPMHCI were analyzed by using the Gini coefficient and the CCD model, and the Grey forecasting model GM (1, 1) (GM) was used to predict the equity and CCD from 2020 to 2022. Between 2013 and 2019, the number of SPMHCI increased from 3.17 million to 3.50 million, and the population-based Gini coefficient declined from 0.0704 to 0.0513. In urban and rural areas, the Gini coefficients decreased from 0.1185 and 0.0737 to 0.1025 and 0.0611, respectively. The CCD between SPMHCI and citizens' living standards (CLS) changed from 0.5691, 0.5813, 0.5818 to 0.5650, 0.5634, 0.6088 at national, urban, and rural levels, respectively. The forecasting results of GM revealed that at the national, urban and rural levels from 2020 to 2022, the Gini coefficient would rise at a rate of - 13.53, - 5.77%, and - 6.10%, respectively, while the CCD would grow at a rate of - 0.89, 1.06, and 0.87%, respectively. In China, the number of SPMHCI has increased significantly, with an equitable allocation based on the population. The interaction between SPMHCI and CLS is sufficient, but the degree of mutual promotion is moderate. The government could optimize SPMHCI and improve the chronic disease management services to improve CLS and to ensure the continued operation of primary medical and health care institutions in urban areas.


[Molecular Therapies of Hereditary Myopathies in Adulthood - a Cursive Overview].
Several types of molecular therapy have become a novel opportunity in the precision treatment of hereditary neuromuscular disorders. This cursive review of gene therapy in hereditary myopathies will focus on selected current phase 1 to 3 trials of common adult hereditary myopathies such as Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, calpainopathy, and dysferlinopathy. The treatment options for Pompe disease serve as an example for hereditary metabolic myopathies.


The pain crisis: what it is and what can be done.
Chronic pain is present in epidemic proportions in most countries, is often unrelieved, and has a huge socioeconomic impact. It is not just a "medical" illness but indeed is a problem that faces all healthcare professional fields. Several steps are identified to address this crisis. These include approaches to enhance pain awareness and access to timely and effective care for pain, and educational and research approaches to improve the knowledge base of healthcare professionals and students and diagnostic and management procedures for pain. Several opportunities to enhance pain understanding, access, and management are also identified.


Bile acid metabolism in familial dysbetalipoproteinaemia: studies in subjects with the apolipoprotein E-2/2 phenotype.
Bile acid kinetics and biliary lipid composition were determined in seven subjects with primary dysbetalipoproteinaemia. They were all homozygous for the apolipoprotein E isoform E-2 and six of them were hyperlipidaemic (type III hyperlipoproteinaemia). With or without hyperlipidaemia, the apo E-2/2 phenotype was associated with increased bile acid formation (mean increase compared with 32 normolipidaemic controls, 43%; P less than 0.025). The biliary lipid composition was not different from that seen in the controls. The results indicate that the uptake by the liver of apo E-containing remnant particles is of importance for the regulation of hepatic cholesterol metabolism in man. It is suggested that hepatic cholesterol synthesis is stimulated in dysbetalipoproteinaemia, and that this leads to a compensatory increase in bile acid synthesis.


High-Throughput Testing of Antibody-Dependent Binding Inhibition of Placental Malaria Parasites.
The particular virulence of Plasmodium falciparum manifests in diverse severe malaria syndromes as cerebral malaria, severe anemia and placental malaria. The cause of both the severity and the diversity of infection outcome, is the ability of the infected erythrocyte (IE) to bind a range of different human receptors through Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of the infected cell. As the var genes encoding the large PfEMP1 antigens are extensively polymorphic, vaccine development strategies are focused on targeting the functional binding epitopes. This involves identification of recombinant fragments of PfEMP1s that induce antibodies, which hinder the adhesion of the IE to a given receptor or tissue. Different assays to measure the blocking of adhesion have been described in the literature, each with different advantages. This chapter describes a high-throughput assay used in the preclinical and clinical development of a VAR2CSA based vaccine against placental malaria.


Masking the Peroxidase-Like Activity of the Molybdenum Disulfide Nanozyme Enables Label-Free Lipase Detection.
Two-dimensional MoS2 nanoparticles (2D-nps) exhibit artificial enzyme properties that can be regulated at bio-nanointerfaces. We discovered that protein lipase is able to tune the peroxidase-like activity of MoS2 2D-nps, offering low-nanomolar, label-free detection and identification in samples with unknown identity. The inhibition of the peroxidase-like activity of the MoS2 2D-nps was demonstrated to be concentration dependent, and as low as 5 nm lipase was detected with this approach. The results were compared with those obtained with several other proteins that did not display any significant interference with the nanozyme behavior of the MoS2 2D-nps. This unique response of lipase was characterized and exploited for the successful identification of lipase in six unknown samples by using qualitative visual inspection and a quantitative statistical analysis method. The developed methodology in this approach is noteworthy for many aspects; MoS2 2D-nps are neither labeled with a signaling moiety nor modified with any ligands for signal readout. Only the intrinsic nanozyme activity of the MoS2 2D-nps is exploited for this detection approach. No analytical equipment is necessary for the visual detection of lipase. The synthesis of the water-soluble MoS2 2D-nps is low costing and can be performed in bulk scale. Exploring the properties of 2D-nps and their interactions with biological materials reveals highly interesting yet instrumental features that offer the development of novel bioanalytical approaches.


Birth outcomes among offspring of women exposed to the September 11, 2001, terrorist attacks.
To evaluate the effects of the September 11, 2001, World Trade Center attacks on birth outcomes. Live singleton births between September 11, 2001, and October 31, 2002, to women enrolled in a World Trade Center Health Registry (the Registry, n=446) were compared with births to women residing more than 5 miles from the World Trade Center (n=49,616). Birth weight, gestational age, low birth weight, and preterm delivery were evaluated using linear and logistic regression. Births before September 11, 2001, were analyzed to assess possible seasonal biases of associations with pregnancy trimester on September 11. Associations of birth outcomes with September 11-related psychologic stress and physical exposures were assessed among births to women within the Registry (n=499). Birth weight and gestational age distributions were similar for births to women enrolled in the Registry and comparison births. Although mean gestational age and birth weight varied with trimester on September 11, a similar association was found among births in previous years, consistent with a seasonal effect not related to exposure. Registry-linked births to mothers with probable posttraumatic stress disorder (n=61) had a higher odds of low birth weight (adjusted odds ratio [OR] 2.49, 95% confidence interval [CI] 1.02-6.08) and preterm delivery (adjusted OR 2.48, 95% CI 1.05-5.84) compared with births to women without posttraumatic stress disorder. Women who lived, worked, or were near the World Trade Center on or soon after September 11 had pregnancy outcomes similar to women residing more than 5 miles away. However, among exposed women, probable posttraumatic stress disorder was associated with low birth weight and preterm delivery. II.


Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas.
Colorectal cancer is the second most common cause of cancer-related mortality in the west. The high incidence and mortality make effective prevention an important public-health and economic issue. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit colorectal carcinogenesis and are among the few agents known to be chemopreventive. Randomised trials have shown that sulindac and celecoxib suppress the development of adenomatous polyps and cause regression of existing polyps in patients with familial adenomatous polyposis (FAP), who have a high risk for developing colorectal cancer. The mechanisms by which NSAIDs inhibit neoplastic growth are not fully known. Two recently reported randomised placebo-controlled trials show a chemopreventive effect of aspirin in populations other than those with FAP (Robert Sandler and colleagues, N Engl J Med 2003; 348: 883-90; John Baron and colleagues, N Engl J Med 2003; 348: 891-99). In the Sandler study 635 patients with colorectal cancer were randomised to receive 325 mg aspirin or placebo daily. After a follow-up of around 31 months, the mean number of adenomas was lower in the aspirin group than in the placebo group, corresponding to a relative risk of any recurrent adenoma in the aspirin group of 0.65. In the Baron study 1121 patients with colorectal adenomas were assigned to receive 81 or 325 mg aspirin or placebo daily. Follow-up colonoscopy, 32 months after the index endoscopy, showed an incidence of one or more adenomas of 38% in the 81 mg aspirin group, 45% in the 325 mg aspirin group, and 47% in the placebo group. Together, these studies indicate a moderate chemopreventive effect of aspirin in populations with an intermediate risk of developing colorectal cancer. WHERE NEXT? The anticancer properties of NSAIDs have been demonstrated in vitro and in animal studies, epidemiological reports, and intervention studies. Several mechanisms through which NSAIDs alter colonic carcinogenesis have been elucidated, including the induction of apoptosis in neoplastic cells, via mechanisms dependent and independent of cyclo-oxygenase. Some studies have suggested an important role for the cell-cycle regulating protein p21 in mediating the chemopreventive effect of sulindac. A decrease in p21 expression may be one of the main oncogenic events in the development of colorectal cancer. Thus p21 could be the molecular link in the chemopreventive effects of NSAIDs.


Implementing Chlamydia screening programs in juvenile correctional settings: the california experience.
To present strategies, methods, and tools for implementing a chlamydia screening program across diverse county juvenile justice systems in California, and to present screening and treatment outcomes of this program. Requirements for juvenile hall participants in a chlamydia screening program were described as well as the administrative structure of program implementation. An assessment of screening using administrative data was conducted. Facilitators and barriers to implementation were identified through interviews with local program coordinators and/or institutional medical and correctional staff. Screening projects were implemented in January 2003 in 15 counties (18 juvenile halls) throughout the state. Among institutions with relevant data, the proportion of female detainees screened for chlamydia rose from 35% preprogram implementation to 66% in 2006. High screening levels with high case yields and treatment rates in the juvenile correctional setting can be accomplished and sustained, despite many barriers, if effective collaboration between public health and correctional entities is established.


The efficacy of bipolar sealer on blood loss in spine surgery: a meta-analysis.
The purpose of this meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to gather data to evaluate the efficacy and safety of bipolar sealer versus standard electrocautery in the management of spinal disease. The electronic databases including Embase, PubMed and Cochrane library were searched to identify relevant studies published from the time of the establishment of these databases up to January 2017. The primary outcomes were total blood loss, requirement of transfusion (rate and amount), and operation time. The secondary outcomes were length of hospital stay and postoperative wound infection. Data analysis was conducted with RevMan 5.3 software. A total of five studies involving 500 patients (261 patients in the BS group and 239 in the control group) were included in the meta-analysis. The pooled results revealed that application of bipolar sealer could decrease the total blood loss in spine surgery [WMD = -467.49, 95% CI (685.47 to -249.51); p < 0.05; I 2 = 91%]. Compared with standard electrocautery, bipolar sealer was associated with lower rates of need for transfusion [OR = 0.30, 95% CI (0.16-0.55), p < 0.05; I 2 = 0%]. In addition, patients in the BS group were likely to receive less amount of blood transfusion compared with patients in the control group[WMD = -0.73, 95% CI (-1.37 to -0.09), p < 0.05; I 2 = 76%]. The mean operative time was shorter in the BS groups compared with the control group [SMD = -0.36, 95% CI (-0.60 to -0.13), p < 0.05; I 2 = 0%]. There was no significant difference in terms of length of hospital stay [WMD = -0.73, 95% CI (-1.96 to 0.51), p = 0.25; I 2 = 67%] and postoperative wound infection [OR = 0.88, 95% CI (0.31-2.48), p = 0.81; I 2 = 0.0%] between both groups. The available evidence suggests that bipolar sealer is superior to standard electrocautery with less blood loss, shorter operation time and less transfusion requirement. There is no significant difference between both groups regarding length of hospitalization and wound infection. Hence, bipolar sealer is recommended in spine surgery. Because of the limitation of our study, more well-designed RCTs with large sample are required to provide further evidence of safety and efficacy between bipolar sealer and standard electrocautery in the treatment of spinal disease.


High Frequency of Imprinted Methylation Errors in Human Preimplantation Embryos.
Assisted reproductive technologies (ARTs) represent the best chance for infertile couples to conceive, although increased risks for morbidities exist, including imprinting disorders. This increased risk could arise from ARTs disrupting genomic imprints during gametogenesis or preimplantation. The few studies examining ART effects on genomic imprinting primarily assessed poor quality human embryos. Here, we examined day 3 and blastocyst stage, good to high quality, donated human embryos for imprinted SNRPN, KCNQ1OT1 and H19 methylation. Seventy-six percent day 3 embryos and 50% blastocysts exhibited perturbed imprinted methylation, demonstrating that extended culture did not pose greater risk for imprinting errors than short culture. Comparison of embryos with normal and abnormal methylation didn't reveal any confounding factors. Notably, two embryos from male factor infertility patients using donor sperm harboured aberrant methylation, suggesting errors in these embryos cannot be explained by infertility alone. Overall, these results indicate that ART human preimplantation embryos possess a high frequency of imprinted methylation errors.


Associations between maternal calcium intake from diet and supplements during pregnancy and the risk of preterm birth in a Chinese population.
Preterm birth is a global public health priority related to maternal nutrition. The effect of maternal calcium intake during pregnancy on preterm birth is inconclusive and data is lacking in China. We aimed to estimate the role of calcium intake from diet and supplements on preterm birth in the Chinese population. We used data of 7195 women from a large-scale cross-sectional study in Northwest China. Dietary intake was evaluated via a validated food frequency questionnaire, and other information was collected by a structured questionnaire. Generalized estimating equation models were used to estimate the relationship between calcium intake and preterm birth. Inadequate dietary calcium intake was universal in our population (85.9%), and no association was found between daily dietary calcium intake and preterm birth. Maternal calcium supplementation was significantly associated with reduced risk of preterm birth (OR 0.72, 95% CI 0.60, 0.87, P = 0.001), particularly among women who commenced calcium supplementation in the second and third trimester of pregnancy with longer duration (OR 0.62, 95% CI 0.42, 0.91, P = 0.015). Higher daily calcium intake from supplements was linked with lower preterm birth risk (every 100 mg increase: OR 0.87, 95% CI 0.79, 0.96, P = 0.004). There is a negative association between daily total calcium intake and preterm birth among calcium supplement users (every 100 mg increase: OR 0.91, 95% CI 0.84, 0.97, P = 0.007). In conclusion, appropriate calcium supplementation during pregnancy could be beneficial in the prevention of preterm birth, and it might be suitable for implementing in low calcium intake areas of China.


Portable X-ray fluorescence for autonomous in-situ characterization of chloride in oil and gas waste.
Soil salinization resulting from anthropogenic activities affects soil health and productivity. Methods that can provide rapid, inexpensive, and accurate salinity characterization over vast areas of soil and waste materials will help in managing their impacts. The objective of this work was to evaluate the accuracy and precision of portable X-ray Fluorescence (pXRF) Cl- measurements of highly saline waste material (WMs) from oil and gas production sites. We compared pXRF Cl- measurements of three unconsolidated WMs to a standard laboratory method for determining soil salinity and identified the WM properties that most affect the precision and accuracy of the pXRF Cl- measurement. Despite covering a range of several orders of magnitude in chloride concentration, calibrated pXRF measurements varied by no more than 14% compared to standard laboratory Cl- measurements for dry homogenous samples. Measurements taken of WMs that were not homogenized decreased pXRF accuracy by 75% while moisture content decreased accuracy by 15%. Field measurements made at different areas inside an oil and gas WM pit were accurate within 60% of the standard laboratory Cl- measurements, despite the samples having a wide range of moisture content and particle size distributions. This study indicates that pXRF can be used to rapidly characterize soil salinity in-situ with acceptable accuracy and precision for screening purposes, opening the door for automated robotic measurements of chloride over large areas.


Regulation by anti-inflammatory cytokines (IL-4, IL-10, IL-13, TGFbeta)of interleukin-8 production by LPS- and/ or TNFalpha-activated human polymorphonuclear cells.
The capacity to down-regulate the production of IL-8 by LPS-activated human polymorphonuclear cells (PMN) has been demonstrated for IL-4, IL-10, and TGFbeta. We compared their relative capacities and further extended this property to IL-13. We report a great heterogeneity among individuals related to the responsiveness of PMN to the IL-4 and IL-13 inhibitory effects while their response to the IL-10 effect was homogenous. The inhibitory activities were observed at the transcriptional level. IL-8 induction by TNFalpha was, unlike its induction by LPS, resistant to the inhibitory effects of IL-10, IL-4, IL-13 and TGFbeta. Furthermore, IL-10 and IL-4 inhibitory activity were less effective when TNFalpha was acting synergistically with LPS to induce IL-8 production by PMN. LPS-induced cell-associated IL-8, detected in the PMN cultures, could be marginally inhibited by IL-4 and IL-10. Altogether, our data demonstrate that IL-13 is able to inhibit LPS-induced IL-8 production by human PMN, although IL-10 remains the most active anti-inflammatory cytokine. Despite the capacity of IL-4, IL-10, and IL-13 to limit the production of TNFalpha-induced IL-8 in a whole blood assay, none was able to inhibit this production when studying isolated human polymorphonuclear cells.


Initiation site of deoxyribonucleotide polymerization at the replication origin of the Escherichia coli chromosome.
A new round of chromosomal replication of a temperature-sensitive initiation mutant (dnaC) of Escherichia coli was initiated synchronously by a temperature shift from a nonpermissive to a permissive condition in the presence of arabinosyl cytosine. Increased amounts of nascent DNA fragments with homology for the chromosomal segment containing the replication origin (oriC) were found. The nascent DNA fragments were purified and treated with alkali to hydrolyze putative primer RNA and to expose 5'-hydroxyl DNA ends at the RNA-DNA junctions. The ends were then labeled selectively with T4 polynucleotide kinase and [gamma-32P]ATP at 0 degrees C and the terminally-labeled initiation fragments were purified by hybridization with origin probe DNAs containing one each of the constituent strands of oriC-DNA segment. The 32P-labeled initiation sites were then located at the resolution of single nucleotides in the nucleotide sequence of the oriC segment after cleavage with restriction enzymes. Two initiation sites of DNA synthesis, 37 nucleotides apart, were detected in one of the component strands of the oriC; in other words, in the strand whose 5' to 3' polynucleotide polarity lies counterclockwise on the E. coli genetic map. The results support the involvement of the primer RNA in the initiation of DNA synthesis at the origin of the E. coli genome and suggest that the first initiation event is asymmetric.


Energy intake and expenditure of free-living, lactating Colombian women in an urban setting.
To examine the components of energy balance during lactation in a population of economically disadvantaged women in an urban developing country setting in order to better understand the metabolic response to lactation. Cross-sectional comparison of lactating (LACT) and non-pregnant non-lactating (NPNL) women. Body size and composition were assessed via anthropometry, energy intake was measured using estimated diet records and energy expenditure using indirect calorimetry and the Flex-Heart Rate method. Low-income neighborhoods of Cali, Colombia. Lactating women (n=15) studied at 2.4+/-0.8, 5.5+/-0.8 and 8.9+/-1.2 months postpartum, and NPNL women (n=48) studied in three measurement rounds at 0, 3.5+/-0.6 and 7.1+/-1.0 months. There were no significant differences between LACT and NPNL women in anthropometric dimensions, but LACT women showed decreases in waist-hip ratio, lean body mass and increases in mid-arm circumference and percentage body fat with time. Energy intake was higher in LACT women (P=0.04), but there were no significant between-group differences in energy expenditure variables. This group of women met the cost of lactation principally via increased energy intake.


A Mixed-Methods Examination of Language Used by College Students to Describe Alcohol Recovery.
Given that approximately 5% of the U.S. population is currently attending college, research is needed to better understand the language that college students use to describe alcohol recovery regardless of their current drinking behavior. College student perceptions of alcohol recovery are important, given that students may experience an alcohol use disorder themselves or may encounter others with an alcohol use disorder. Research on college student perceptions of alcohol recovery in the literature is scarce but is needed to better understand the alcohol recovery process. The current mixed-methods study examines language that college students use to describe alcohol recovery based on findings from two focus group interviews. The focus groups were conducted with college students who reported using alcohol at least once in their lifetime. All participants (N = 18) were asked questions regarding language perceived to be associated with alcohol recovery. Data were examined within a thematic analysis framework. The three central themes related to alcohol recovery that emerged in the study were harm reduction-based recovery, abstinence-based recovery, and social correlates of recovery. College students rated the terms "recovered," "drinking reduction," and "sobriety" as being highly representative of being in recovery, whereas the terms "bars" and "light drinker" were identified as not being representative of recovery. A better understanding of these themes will help the field understand the language that college students use to describe alcohol recovery.


Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019.
Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.


Prevalence of HIV/AIDS Infection among Sexually Active Women in Ethiopia: Further Analysis of 2016 EDHS.
The issue of HIV/AIDS is prevalent around the world and in Ethiopia as well. The aim of this study was to determine the prevalence and risk factors of HIV/AIDS infection among sexually active women in Ethiopia. For this study, data were obtained from the Ethiopia Demographic and Health Survey conducted in 2016. This study contains 11,729 women who have had at least one episode of sexual intercourse in their lifetime. Interviewers for voluntary HIV testing collected finger-prick blood specimens from women who agreed to be tested for HIV. Based on factors at the individual and community levels, a multilevel logistic regression model was used. The study found that 2% of 11,729 sexually active women tested positive for HIV from all regions who received voluntary counseling and testing. The intraclass correlation coefficient findings showed that 32.844% of HIV/AIDS transmission among sexually active women was the result of community-level factors. Variables at the individual level were women of age 16-24 (AOR = 0.18; 95% CI: 0.11-0.29), women of age 25-34 (AOR = 0.733; 95% CI: 0.55-0.98), women with primary education level (AOR = 1.8; 95% CI: 1.23-2.57), more than one sexual accomplice (AOR = 1.33; 95% CI: 0.613-2.87), and women's age at first sexual intercourse between 25 and 34 (AOR = 0.57, 95% CI: 0.301, 1.06); these were the most significant determinants of HIV/AIDS infection. According to community-level factors, there was a lower HIV prevalence rate among rural women (AOR = 0.22; 95 percent CI: 0.13-0.36), and women in the Gambela region (AOR = 4.1; 95 percent CI: 1.99-8.34) also had higher HIV prevalence rates. The prevalence of HIV infection among sexually active women varies by region, with urban women more likely to contract the virus. Women who had more than one regular sexual partner and had their first sexual encounter at a younger age are at an increased risk of contracting HIV/AIDS. According to the study, the government should focus more support on high-risk clusters, mainly in urban areas, as well as on regions with high rates of HIV/AIDS infection.


Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection.
The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1-/- and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.


Mycobacterium ulcerans in the Elderly: More Severe Disease and Suboptimal Outcomes.
The clinical presentation of M. ulcerans disease and the safety and effectiveness of treatment may differ in elderly compared with younger populations related to relative immune defficiencies, co-morbidities and drug interactions. However, elderly populations with M. ulcerans disease have not been comprehensively studied. A retrospective analysis was performed on an observational cohort of all confirmed M. ulcerans cases managed at Barwon Health from 1/1/1998-31/12/2014. The cohort included 327 patients; 131(40.0%) ≥65 years and 196(60.0%) <65 years of age. Patients ≥65 years had a shorter median duration of symptoms prior to diagnosis (p<0.01), a higher proportion with diabetes (p<0.001) and immune suppression (p<0.001), and were more likely to have lesions that were multiple (OR 4.67, 95% CI 1.78-12.31, p<0.001) and WHO category 3 (OR 4.59, 95% CI 1.98-10.59, p<0.001). Antibiotic complications occurred in 69(24.3%) treatment episodes at an increased incidence in those aged ≥65 years (OR 5.29, 95% CI 2.81-9.98, p<0.001). There were 4(1.2%) deaths, with significantly more in the age-group ≥65 years (4 compared with 0 deaths, p = 0.01). The overall treatment success rate was 92.2%. For the age-group ≥65 years there was a reduced rate of treatment success overall (OR 0.34, 95% CI 0.14-0.80, p = <0.01) and when surgery was used alone (OR 0.21, 95% CI 0.06-0.76, p<0.01). Patients ≥65 years were more likely to have a paradoxical reaction (OR 2.06, 95% CI 1.17-3.62, p = 0.01). Elderly patients comprise a significant proportion of M. ulcerans disease patients in Australian populations and present with more severe and advanced disease forms. Currently recommended treatments are associated with increased toxicity and reduced effectiveness in elderly populations. Increased efforts are required to diagnose M. ulcerans earlier in elderly populations, and research is urgently required to develop more effective and less toxic treatments for this age-group.


Bacterially mediated drug delivery and therapeutics: Strategies and advancements.
It was already clinically apparent 150 years ago that bacterial therapy could alleviate diseases. Recently, a burgeoning number of researchers have been using bacterial regimens filled with microbial therapeutic leads to diagnose and treat a wide range of disorders and diseases, including cancers, inflammatory diseases, metabolic disorders and viral infections. Some bacteria that were designed to have low toxicity and high efficiency in drug delivery have been used to treat diseases successfully, especially in tumor therapy in animal models or clinical trials, thanks to the progress of genetic engineering and synthetic bioengineering. Therefore, genetically engineered bacteria can serve as efficient drug delivery vehicles, carrying nucleic acids or genetic circuits that encode and regulate therapeutic payloads. In this review, we summarize the development and applications of this approach. Strategies for genetically modifying strains are described in detail, along with their objectives. We also describe some controlled strategies for drug delivery and release using these modified strains as carriers. Furthermore, we discuss treatment methods for various types of diseases using engineered bacteria. Tumors are discussed as the most representative example, and other diseases are also briefly described. Finally, we discuss the challenges and prospects of drug delivery systems based on these bacteria.


An Electrochemical Perspective on the Interfacial Width between Two Immiscible Liquid Phases.
Molecular dynamics simulations and vibrational sum-frequency spectroscopy are historically the main techniques applied to the description of the molecular structure and dynamics of the immiscible liquid/liquid interface. A molecular sharpness is estimated for oil/water interfaces, with an interfacial width that extends from hundreds of Å to 1 nm. However, electrochemical studies have elucidated a deeper liquid/liquid interface on the order of several micrometers. The breaking down of single-entity electrochemistry to simpler systems and the combination of high-resolution microscopies is confirming a larger extension of the interface. What can be the role of the electrochemist in clarifying this fundamental question? We try to give a suggestion at the end of a brief historical overview of the liquid/liquid interface studies.


Development of diagnostic reference frames for seizures. Part 2: are seizure descriptions discriminative?
To determine whether the seizure descriptions given by a group of neurologists/epileptologists are discriminative. We constructed templates for various seizure types describing how often symptoms were selected by the participants. We defined a matching score to indicate the match between such a template and the symptoms selected by each neurologist/epileptologist individually and computed the scores for each of the sets of selected symptoms with all templates. Correlation coefficients were calculated between the templates. Data were collected from 24 participants. The matching scores and the correlation coefficients both show that participants provide discriminative descriptions of the seizure types. Descriptions of aggregated seizure types, such as primary generalized seizures, are less discriminatory than the descriptions of more specific seizure types. We concluded that the participants in our study selected symptoms that result in discriminative descriptions of the seizure types. This indicates that knowledge elicitation by using the opinions of a group of clinical experts is possible. The study also indicates that the design of the study could be ameliorated in several ways. These findings will be taken into account when designing the final study.


Differential susceptibility between skin and vaginal mucosa in sensitization phase of allergic contact dermatitis in mice.
Mechanisms underlying skin sensitization in allergic contact dermatitis have been actively studied using the murine contact hypersensitivity (CHS) model. However, much less is known about sensitization at the vaginal mucosa (VM). We developed a CHS model with VM sensitization and epicutaneous elicitation at the ear. We then examined the proliferation activity of lymphocytes, the frequencies of T cells and the differentiation of hapten-specific T cells in draining lymph nodes (dLNs) after sensitization. Hapten-specific CHS responses to 2,4-dinitrofluorobenzene (DNFB), 2,4,6-trinitrochrolobenzene, and oxazolone assessed by ear swelling suggested that the VM would be an inductive site of CHS to haptens. In the comparisons of CHS responses to each of the three haptens examined, the lower responses in VM-sensitized mice were observed than skin-sensitized mice (e.g., DNFB-induced responses, -56%; p < .001, at 48 h after challenge). Consistent with the CHS responses, the DNFB-induced proliferation of cells in dLNs examined by 5-bromo-2'-deoxyuridine assay was lower (-62%; p < .001) in VM-sensitized mice than skin-sensitized mice. On the other hand, between skin and VM sensitization, no significant differences were observed in the frequencies of interferon-γ-producing CD4+ and CD8+ effector, and regulatory T cells in dLNs after sensitization. We also observed no significant differences with respect to differentiation of hapten-specific T cells based on the examination of cytokine production from dLN cells stimulated in vitro with 2,4-dinitrobenzene sulfonate. These findings suggested that the lower T cell proliferation after VM sensitization is important for the lower CHS responses with VM sensitization than skin sensitization.


The BTG2 protein is a general activator of mRNA deadenylation.
BTG2 is a prototype member of the BTG/Tob family of antiproliferative proteins, originally identified as a primary response gene induced by growth factors and tumour promoters. Its expression has been linked to diverse cellular processes such as cell-cycle progression, differentiation or apoptosis. BTG2 has also been shown to interact with the Pop2/Caf1 deadenylase. Here, we demonstrate that BTG2 is a general activator of mRNA decay, thereby contributing to gene expression control. Detailed characterizations of BTG2 show that it enhances deadenylation of all transcripts tested. Our results demonstrate that Caf1 nuclease activity is required for efficient deadenylation in mammalian cells and that the deadenylase activities of both Caf1 and its Ccr4 partner are required for Btg2-induced poly(A) degradation. General activation of deadenylation may represent a new mode of global regulation of gene expression, which could be important to allow rapid resetting of protein production during development or after specific stresses. This may constitute a common function for BTG/Tob family members.


The role of posterior lumbotomy in the management of surgical stone disease.
A total of 50 consecutive patients underwent posterior lumbotomy for removal of upper third ureteral or renal pelvic stones between June 1983 and October 1986. Morbidity was low, hospitalization was brief and 100 per cent of the patients were rendered free of stones postoperatively. Dorsal lumbotomy compares favorably with other currently available methods for the management of selected patients with calculous disease.


Effect of covalent links on the structure, spectra, and redox properties of myeloperoxidase--a density functional study.
The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe(II)) and oxidized (Fe(III)) states, as well as in the compound I (formally Fe(V)O) and II (Fe(IV)O or Fe(IV)OH) states, using appropriate models of the linkages to the Asp, Glu, and Met residues (including the back-bone connection between Glu-242 and Met-243) in varying combinations. The calculated spectral shifts indicate that both the ester and sulfonium linkages play a role in the spectral shift. On the other hand, the sulfonium linkage seems to be mainly responsible for the high positive reduction potential for the both ferric/ferrous and compound I/II couples of myeloperoxidase.


Inhibition of melanogenesis as an adjuvant strategy in the treatment of melanotic melanomas: selective review and hypothesis.
Melanogenesis generates immunosuppressive and mutagenic environment and alters cellular metabolism. Melanin can protect malignant melanocytes against chemo-, radio-, and photodynamic therapy. Therefore, we propose to inhibit melanogenesis as an adjuvant treatment modality during immuno-, radio-, chemo- and photodynamic therapy, and as a measure of reducing the probability of melanoma progression.


Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.
Microtubule targeting agents (MTAs) are anticancer therapies commonly prescribed for breast cancer and other solid tumors. Sensory peripheral neuropathy (PN) is the major dose-limiting toxicity for MTAs and can limit clinical efficacy. The current pharmacogenomic study aimed to identify genetic variations that explain patient susceptibility and drive mechanisms underlying development of MTA-induced PN. A meta-analysis of genomewide association studies (GWAS) from two clinical cohorts treated with MTAs (Cancer and Leukemia Group B (CALGB) 40502 and CALGB 40101) was conducted using a Cox regression model with cumulative dose to first instance of grade 2 or higher PN. Summary statistics from a GWAS of European subjects (n = 469) in CALGB 40502 that estimated cause-specific risk of PN were meta-analyzed with those from a previously published GWAS of European ancestry (n = 855) from CALGB 40101 that estimated the risk of PN. Novel single nucleotide polymorphisms in an enhancer region downstream of sphingosine-1-phosphate receptor 1 (S1PR1 encoding S1PR1 ; e.g., rs74497159, βCALGB 40101 per allele log hazard ratio (95% confidence interval (CI)) = 0.591 (0.254-0.928), βCALGB 40502 per allele log hazard ratio (95% CI) = 0.693 (0.334-1.053); PMETA = 3.62 × 10-7 ) were the most highly ranked associations based on P values with risk of developing grade 2 and higher PN. In silico functional analysis identified multiple regulatory elements and potential enhancer activity for S1PR1 within this genomic region. Inhibition of S1PR1 function in induced pluripotent stem cell-derived human sensory neurons shows partial protection against paclitaxel-induced neurite damage. These pharmacogenetic findings further support ongoing clinical evaluations to target S1PR1 as a therapeutic strategy for prevention and/or treatment of MTA-induced neuropathy.


Photosynthetic gas exchange under emersed conditions in eulittoral and normally submersed members of the Fucales and the Laminariales: interpretation in relation to C isotope ratio and N and water use efficiency.
Ten species of brown macroalgae (five eulittoral and one submersed species of the Fucales; four submersed species of the Laminariales) from a rocky shore at Arbroath, Scotland, were examined for characteristics of emersed photosynthesis in relation to the partial pressure of CO2 and O2. The five eulittoral species of the Fucaceae were approaching CO2 saturation for light-saturated photosynthesis at normal air levels of CO2 (35 Pa) in 21 kPa O2. The normally submersed algae are further from CO2 saturation under these conditions, especially in the case of the four members of the Laminariales. The rate of net photosynthesis in the Fucaceae is O2-independent in the range 2-21 kPa O2 over the entire range of CO2 partial pressure tested (compensation up to 95 Pa). For the other five algae tested, net photosynthesis is slightly inhibited by O2 at 21 kPa relative to 2 kPa over the entire range of CO2 partial pressures tested (compensation up to 95 Pa). CO2 compensation partial pressures are low (<0.5 Pa) for the Fucaceae and independent of O2 in the range 2-42 kPa. For the other five algae, the CO2 compensation partial pressure are higher, and increased with O2 partial pressure in the range 2-42 kPa. These gas exchange data show that the Fucaceae exhibit more C4-like characteristics of their photosynthetic physiology than do the other five species tested, although even the Laminariales and Halidrys siliquosa are not classic C3 plants in their photosynthetic physiology. These data suggest that, in emersed conditions as well as in the previously reported work on submersed photosynthesis, a "CO2 concentrating mechanism" is operating which, by energized transmembrane transport of inorganic C, accumulates CO2 at the site of RUBISCO and, at least in part, suppresses the oxygenase activity. Work with added extracellular carbonic anhydrase (CA), and with a relatively membrane-impermeant inhibitor of the native extracellular CA activity (acetazolamide), suggests that, in emersed conditions as well as in the previously reported work on algae submersed in seawater at pH 8, HCO inf3sup- is the major inorganic C species entering the cell. At optimal hydration, the rate of emersed photosynthesis in air is not less than the rate of photosynthesis when submersed in seawater, at least for the Fucaceae. δ13C ratios of organic C for the Fucaceae are slightly more negative than is the case for the other five algae; these data are consitent with substantial (half or more of the entering inorganic C) leakage of CO2 from the accumulated pool, and with some contribution of atmospheric CO2 to the organic C gain by the eulittoral algae. The predicted increase in N use efficiency of photosynthesis in the Fucaceae, with their more strongly developed CO2 concentrating mechanism, is consistent with data on emersed, but not submersed, photosynthesis for the algae collected from the wild and thus at a poorly defined N status. The more C4-like gas exchange charateristics of photosynthesis in the eulittoral Fucaceae may be important in increasing the water use efficiency of emersed photosynthesis from the limited capital of water available for transpiration by a haptophyte.


Enhancement of dorsal raphe discharge by medial pontine reticular formation stimulation depends on behavioral state.
Single cell activity was recorded with microwire electrodes from the dorsal raphe nucleus (DRN) of cats across multiple cycles of sleep and wakefulness. Electrical stimulation of the medial pontine reticular formation (mPRF) produced a 10-fold enhancement of DRN discharge during wakefulness and slow wave sleep but not during desynchronized sleep. The neuronal mechanisms likely to mediate the state-dependent effects of mPRF stimulation are discussed with regard to the hypothesis that DRN plays a major role in behavioral state control.


Memory-related cognitive load effects in an interrupted learning task: A model-based explanation.
The Cognitive Load Theory provides a well-established framework for investigating aspects of learning situations that demand learners' working memory resources. However, the interplay of these aspects at the cognitive and neural level is still not fully understood. We developed four computational models in the cognitive architecture ACT-R to clarify underlying memory-related strategies and mechanisms. Our models account for human data of an experiment that required participants to perform a symbol sequence learning task with embedded interruptions. We explored the inclusion of subsymbolic mechanisms to explain these data and used our final model to generate fMRI predictions. The final model indicates a reasonable fit for reaction times and accuracy and links the fMRI predictions to the Cognitive Load Theory. Our work emphasizes the influence of task characteristics and supports a process-related view on cognitive load in instructional scenarios. It further contributes to the discussion of underlying mechanisms at a neural level.


Enhancement of tumorigenicity and invasion capacity of rat mammary adenocarcinoma cells by epidermal growth factor and transforming growth factor-beta.
We have studied the effects of growth factors and cytokines on the tumorigenicity and invasion capacity of tumor cells by using regressor and progressor tumor cell lines (ER-1 and ERpP, respectively) derived from an SHR rat mammary adenocarcinoma. ER-1 cells regress spontaneously whereas ERpP cells show invasive growth and high metastasis to lung and other organs in syngeneic SHR rats. When ER-1 cells were pretreated with either epidermal growth factor (EGF) or transforming growth factor-beta (TGF-beta) for 24 h in vitro, and intraperitoneally transplanted into SHR rats, they grew and killed the host, whereas ER-1 cells pretreated with tumor necrosis factor-alpha did not. Tumorigenicity and invasion capacity of ERpP cells were also enhanced by treatment with EGF and TGF-beta. The ER-1 cells pretreated with EGF, once grown in vivo, had acquired irreversible tumorigenicity and invasion capacity without requiring further EGF treatment, and the enhanced malignancy was irreversible. These findings suggest that growth factors play an important role in acquisition of malignancy of tumor cells.


Studies on normal human skeletal muscle in relation to the pathopharmacology of malignant hyperpyrexia.
1. The effects of dantrolene on pharmacologically-induced contractures and potentiated isometric twitches in normal human skeletal muscle have been studied in vitro. 2. Dantrolene sodium, at concentrations of 3 mumol/l or less, attenuates basal twitch, inhibits halothane potentiation of basal twitch and inhibits halothane-potentiated potassium contractures, but has less effect on twitch potentiation by 2 mmol/l caffeine. 3. Caffeine contractures are attenuated by dantrolene concentrations of 12 mumol/l or greater. The effect of dantrolene on caffeine contracture is characterized by decreased contracture tension and by prolonged time to peak contracture. 4. The results indicate that halothane and 2 mmol/l caffeine have agonistic effects on the excitation-contraction (E-C) coupling mechanism, and suggest that they may act at separate E-C coupling sites. The relationships of these findings to the pathopharmacology of malignant hyperpyrexia are discussed.


Sal-like 4 (SALL4) suppresses CDH1 expression and maintains cell dispersion in basal-like breast cancer.
In cell cultures, the dispersed phenotype is indicative of the migratory ability. Here we characterized Sal-like 4 (SALL4) as a dispersion factor in basal-like breast cancer. Our shRNA-mediated SALL4 knockdown system and SALL4 overexpression system revealed that SALL4 suppresses the expression of adhesion gene CDH1, and positively regulates the CDH1 suppressor ZEB1. Cell behavior analyses showed that SALL4 suppresses intercellular adhesion and maintains cell motility after cell-cell interaction and cell division, which results in the dispersed phenotype. Our findings indicate that SALL4 functions to suppress CDH1 expression and to maintain cell dispersion in basal-like breast cancer.


Limitation of resistance as a parameter by which to characterize epithelia that actively transport ions.
It is theoretically inappropriate to characterize an actively transporting epithelim by "resistance" alone which is correctly applied only to passive circuit elements. Rather, such epithelia (if they actively transport sodium) required, as a minimum, characterization by an active circuit element parameter such as voltage (E Na), current (I Na) or power (WNa) in some configuration with resistances. Recent experimental studies of epithelia which actively transport sodium have omitted consideration of the active circuit element and attributed all measured changes observed to "resistance" changes in the epithelium as the transepithelial sodium gradient is altered. It is suggested that the observed changes in voltage/current ratio could be consequences of changes in the electrical behavior of the active circuit element of such epithelia. It may be biologically impossible to suppress all electromotive forces in epithelia to measure the truly passive characteristics of the epithelim without destroying tissue viability. The actual methods used to date for measurement of "resistance" in epithelia consist of perturbing signals which might alter the electrical behavior of an active element such as an "ion pump"; the observed changes in voltage to current ratio observed in such experiments can be better explained by a change in the active ion pump rather than by changes in passive epithelial "resistance".


Single-ventricle physiology reduces cerebral oxygen delivery in a piglet model.
In single-ventricle physiology, cerebral blood flow and oxygen (O2) delivery may be inadequate. This study tests the hypotheses that in acute univentricular physiology (1) cerebral blood flow increases inadequately to maintain O2 delivery, (2) the brain is incapable of increasing O2 extraction due to hypoxemia, and (3) cerebral O2 delivery diminishes selectively in different brain regions. Univentricular physiology was created in 8 piglets, while 8 animals were sham controls. Aortopulmonary shunt, echocardiography-guided atrial septostomy, tricuspid valve avulsion, and pulmonary artery occlusion were performed to allow the left ventricle to support systemic and pulmonary circulations. Cerebral blood flow (microspheres), cerebral O2 and lactate metabolism, and cerebral O2 saturation were measured at baseline, 30 minutes, and 120 minutes after conversion to univentricular physiology. Cerebral blood flow increased in the cerebrum and subtentorium in controls (p < 0.05), whereas it remained unchanged in univentricular piglets. Cerebral O2 delivery at 30 and 120 minutes was lower in univentricular physiology than in controls (p = 0.05). Fractional oxygen extraction was unchanged in both groups. Cerebral O2 consumption trended lower in univentricular physiology (p = not significant), while it was unchanged in controls. Lactate cerebral metabolic rate (CMRLactate) increased at 30 and 120 minutes in both groups. The decline in O2 delivery was variable, but present in nearly all brain regions. This study confirms the hypothesis that, in univentricular physiology, hypoxemia and limited cerebral blood flow reduce cerebral O2 availability in nearly all regions. These findings contribute to the understanding of brain abnormalities in infants with univentricular physiology.


Late failure of porcine valve heterografts in children.
Heterograft porcine valves have gained wide acceptance in replacement of diseased cardiac valves, and their clinical performance in adults has been very satisfactory over follow-up periods of up to 8 years. Valve replacement in children is relatively infrequent and experience with porcine xenografts is necessarily small. Our combined experience at three university hospitals has been with 25 children, 17 months to 16 years of age, who have been followed for 10 to 54 months (mean follow-up 33 months). Porcine valves were used to replace the aortic valve in nine, the mitral valve in seven, both valves in two, the tricuspid valve in two, and the pulmonary valve in five patients. Severe bioprosthetic valve dysfunction has occurred in five (20%) of these patients so far and necessitated replacement because of severe stenosis in mitral (two) or aortic (three) valve prostheses at 18 to 45 months after implantation; one postoperative death occurred among the five reoperations. Pathological examination showed extensive fragmentation of collagen with focal heavy calcification and degeneration. In addition we have encountered deterioration and calcification of two porcine valves in 23 valved conduits followed for 12 to 70 months (mean 43 months), requiring removal and replacement of the valves 65 and 67 months after implantation. This experience indicates a disquietingly high incidence of relatively early failure of porcine xenograft valves in children. This is significantly higher than the failure rate observed in adult patients. The failure rate is not consistently related to the small size of an implanted valve which becomes relatively narrow with the growth of the patient, leading to excessive turbulence and trauma to the prosthesis. Other factors, including increased turnover of calcium and accelerated rejection in growing children, may contribute to these failures and should be examined in order to improve long-term results. A satisfactory performance would make heterografts the ideal valvular prosthesis in children, since anticoagulation is avoided.


Improving athletes' perspectives of sport psychology consultation: a controlled evaluation of two interview methods.
Although investigations have consistently demonstrated the effectiveness of sport psychology interventions, these methods have been underutilized by athletes. In this study, 124 athletes completed the athletes' Attitudes Toward Seeking Sport Psychology Consultation Questionnaire (ATSSPCQ) and were subsequently randomly assigned to receive one of the two semistructured interview formats. One interview focused on discussing the athlete's experiences in sports, and the other focused on delineating sport psychology and its potential benefits to the athlete. Upon being interviewed, athletes were readministered the ATSSPCQ. Discussing sport psychology and its personal benefits was more effective in enhancing athletes' perception of need for sport psychology than discussing sport experiences. However, neither interview format enhanced athletes' perceptions of openness to discuss personal issues with a sport psychology consultant and tolerance of stigma associated with sport psychology consultation. Indeed, participants who received the discussion of sports intervention reported a significant decrease in personal openness to discuss personal issues relevant to sports psychology from pre- to postintervention. Intervention effects were similar for male and female athletes. Study implications and future directions are discussed in light of these results.


Cocci and diphtheroids in blood cultures from patients in various pathological situations.
The evolution of cocci and diphtheroids taking origin from cell-wall-deficient forms seems not to be related to a particular state of illness, but to be the consequence of a generalized crypto-infection.


Tenascin-C promotes cell survival by activation of Akt in human chondrosarcoma cell.
Tenascin-C (TnC) is an extracellular matrix protein that is highly expressed in tumor stroma. In this report, we examined the roles of TnC-mediated cell adhesion in the modulation of chondrosarcoma cell survival. We found that hTnC-mediated adhesion could confer a significant (P<0.05) survival advantage to human chondrosarcoma cell line, JJ012, following serum-deprivation compared with the same cells grown on poly-lysine. This pro-survival signal was due to the activation of the Akt upon adhesion to hTnC. Moreover, hTnC-induced Akt activation was blocked by LY294002 and the expression of dominant-negative Akt. Taken together, these studies support that the TnC-mediated adhesion can promote cell survival through Akt in human chondrosarcoma cells.


Normalization of Cardiac Function After Bariatric Surgery Is Related to Autonomic Function and Vitamin D.
Subclinical cardiac dysfunction is common in patients with obesity. Bariatric surgery is associated with normalization of subclinical cardiac function in 50% of the patients with obesity. The aim of this study was to identify predictors for a lack of improvement of subclinical cardiac dysfunction 1-year post-bariatric surgery. Patients who were referred for bariatric surgery were enrolled in a longitudinal study. Inclusion criteria were age 35-65 years and BMI ≥ 35 kg/m2. Patients with a suspicion of or known cardiovascular disease were excluded. Conventional and advanced echocardiography, Holter monitoring, and blood tests were performed pre- and 1-year post-bariatric surgery. Subclinical cardiac dysfunction was defined as either a reduced left ventricular ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, arrhythmia, or an increased BNP or hs Troponin I. A total of 99 patients were included of whom 59 patients had cardiac dysfunction at baseline. Seventy-two patients completed the 1-year follow-up after bariatric surgery. There was a significant reduction in weight and cardiovascular risk factors. Parameters of cardiac function, such as GLS, improved. However, in 20 patients cardiac dysfunction persisted. Multivariate analysis identified a decreased heart rate variability (which is a measure of autonomic function), and a decreased vitamin D pre-surgery as predictors for subclinical cardiac dysfunction after bariatric surgery. Although there was an overall improvement of cardiac function 1-year post-bariatric surgery, autonomic dysfunction and a decreased vitamin D pre-bariatric surgery were predictors for a lack of improvement of subclinical cardiac dysfunction.


Germinal mosaicism in Duchenne muscular dystrophy.
We have identified a Duchenne muscular dystrophy (DMD) pedigree where the disease is associated with a molecular deletion within the DMD locus. We have examined the meiotic segregation products of the common female ancestor using marker restriction fragment length polymorphisms (RFLPs) detected by probes that lie within this deletion. These studies show that this female has transmitted three distinct types of X chromosome to her offspring. This observation may be explained by postulating that the mutation arose as a postzygotic deletion within this common ancestor, who was consequently germinally mosaic.


Internal representations underlying respiration during object manipulation.
We examined the presence of anticipatory control and the resulting interactions of the respiratory and motor systems during discrete object manipulation. In response to an auditory signal, subjects reached forward, grasped, and lifted an instrumented object weighing 150 or 1000 g while the breathing pattern, fingertip forces, and movements were measured. Following every block of five lifts, the object was removed from sight and replaced with the same or an alternate mass. Thus, the object's weight was predictable during the last lift of each block and unpredictable during the first lift after the transition. When the object's weight was predictable, the force application was faster and inspiratory duration and the tidal volume were reduced for the breath associated with the lift for 1000-g compared to 150-g lifts. Following the transition, when the object's weight was unpredictable, the force application reflected the weight of the object during the previous lift while the respiratory output, regardless of the preceding weight, resembled that used for 1000-g lifts. Additionally, inspiratory duration was significantly correlated with the reach duration in three of the four unpredictable lifting conditions. We conclude that these system-specific anticipatory alterations may arise from a common internal representation that was formed through past manipulatory weight experience.


Mathematical model of L5178Y mouse lymphoma forward mutation assay.
A mathematical model of the biological protocol for the Mouse Lymphoma L5178Y Forward Mutation Bioassay is presented. The model relates the mutant progenitor frequency (MPF), the number of cells per million surviving cells with DNA damage after exposure to the chemical, to the mutant frequency (MF), the number of TFT-resistant cells per million survivors. For a given expression time, the deterministic relationship is linear and the proportionality constant depends on the relative suspension growth factor (rg) and relative cloning efficiencies (rc) of mutants to those of wild type cells: MF = (rg X rc) X MPF. Experimental noise leads to variations in the values of rg and rc and lack of reproducibility in the system. If mutant progenitors and their progeny grow as well as wild-type cells and if all of the parental mutant progenitors express the mutant phenotype, then rg = 1/2 and rc = 1. Biological mechanisms, such as differential growth characteristics of mutant and wild-type cells or DNA repair, can make the mutant frequency an inaccurate estimate of the MPF. For the assay to be useful as a screen for the mutagenic activity of chemicals, rg X rc has to be reasonably constant from chemical to chemical.


Identification of discrete regions of activity using correlation coefficient scanning of distributed current maps.
Biomagnetic measurements of the brain are often analysed in terms of a number of discrete primary generators. In this paper we describe an objective method of identifying the number of approximate location of such generators. The method is based on the matching of an instrument-independent representation of the data with a template whose pattern is characteristic of a localized primary source. The method is shown to be insensitive to severe noise and to be capable of resolving closely spaced generators.


Metal- and solvent-free synthesis of amides using substitute formamides as an amino source under mild conditions.
This study described an efficient and practical approach for amide synthesis. The reaction was conducted under metal- and solvent-free conditions at a mild temperature (40 °C) in air, and readily available formamides were used as an amino source. This reaction can be easily upgraded to the gram level with an excellent yield.