Improving the primary management of emergency surgical admissions: a controlled trial.
The initial screening by senior surgical staff of surgical patients referred for emergency hospital admission should result in improved patient management. The present study was undertaken to determine the effects of this policy. The primary outcome measure was hospital admission rates. The number of operations, diagnostic investigations, initial treatments, deaths, length of stay and bed days per 100 referrals were also measured. The results suggest a 20 per cent reduction in emergency surgical admissions, an important potential benefit to the health service, and to individual patients.


Development of chitosan-collagen hydrogel incorporated with lysostaphin (CCHL) burn dressing with anti-methicillin-resistant Staphylococcus aureus and promotion wound healing properties.
Methicillin-resistant Staphylococcus aureus (MRSA) have become increasingly prevalent as nosocomial pathogens, especially in burn patients, which is the leading cause of their death. A drug delivery system of chitosan-collagen hydrogel incorporated with lysostaphin (CCHL) based on the lysostaphin gauze was developed for MRSA infected burn wounds. CCHL scaffold consisted of numerous interconnected sphericles and tubular bodies with an average diameter of 100-200 µm, 20-60-fold swelling, high water retention capacity, and cell proliferation properties. The minimal inhibitory concentration of CCHL was 0.053 U/mL. By the second week after its application on MRSA infected third-degree burn wounds, no bacteria could be detected and the burn wounds had started healing. Therefore, CCHL should be studied further as a promising candidate of burn treatment dressing against MRSA infections for clinics.


Modulation of fatty acids oxidation in heart failure by selective pharmacological inhibition of 3-ketoacyl coenzyme-A thiolase.
A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the heart. Pharmacological agents that directly inhibit fatty acid oxidation include inhibitors of 3-ketoacyl coenzyme A thiolase (3-KAT), the last enzyme involved in ss-oxidation. The most extensively investigated agents of this group of drugs are trimetazidine and ranolazine. Clinical studies have shown that these agents can substantially increase the ischemic threshold in patients with effort angina. However, the results of current research is also supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism by 3-KAT inhibitors could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial effects of this new class of drugs on left ventricular dysfunction and glucose metabolism is reviewed and discussed.


A calixarene dendron with surface congestion at the first generation.
The X-ray structure of a dendrimeric receptor based on calixarenes showed a packed periphery in the first generation. The presence of urea groups as linkers between the calix[4]arene core and the calix[6]arene dendrons makes it a good model as an endo-receptor which is able to coordinate squarate dianions with a high association constant.


Fertilizing capacity of epididymal and testicular sperm using intracytoplasmic sperm injection (ICSI).
For men with uncorrectable obstructive azoospermia, their only hope of fathering a child is microsurgical epididymal sperm aspiration (MESA) combined with in vitro fertilization (IVF). In 1988, proximal epididymal sperm were demonstrated to have better motility than senescent sperm in the distal epididymis, and it was thought that retrieval of motile sperm from the proximal epididymis would yield reliable fertilization and pregnancy rates after conventional IVF. However, the results to date have been poor, and although a minority of patients achieved good fertilization rates with IVF, the vast majority (81%) had consistently poor or no fertilization and the pregnancy rate averaged only 9%. Recently, intracytoplasmic sperm injection (ICSI) has been successfully used to achieve fertilization and pregnancies for patients with extreme oligoasthenozoospermia. ICSI has therefore been applied to cases of obstructive azoospermia and, in this report, 67 MESA-IVF cases are compared with 72 MESA-ICSI cases. The principle that motile sperm from the proximal segments of the epididymis should be used for ICSI was followed, although in the most severe cases in which there was an absence of the epididymis (or absence of sperm in the epididymis), testicular sperm were obtained from macerated testicular biopsies. These sperm only exhibited a weak, twitching motion. In 72 consecutive MESA cases, ICSI resulted in fertilization and normal embryos for transfer in 90% of the cases, with an overall fertilization rate of 46%, a cleavage rate of 68%, and ongoing or delivered pregnancy rates of 46% per transfer and 42% per cycle. The pregnancy and take-home baby rates increased from 9% and 4.5% with IVF to 53% and 42% with ICSI. There were no differences between the results for fresh epididymal, frozen epididymal or testicular sperm, and the number of eggs collected did not affect the outcome. The results were also unaffected by the aetiology of the obstruction such as congenital absence of the vas deferens or failed vasoepididymostomy. The only significant factor which affected the pregnancy rate was female age. It is concluded that although complex mechanisms involving epididymal transport may be beneficial for conventional fertilization of human oocytes (in vivo or in vitro), none of these mechanisms are required for fertilization after ICSI. Given the excellent results with epididymal and testicular sperm, ICSI is obligatory for all future MESA patients. Finally, the use of ICSI with testicular sperm from men with non-obstructive azoospermia is also discussed.


Head injury caused by an ostrich: A rare entity.
Human injuries caused by animals are not uncommon and have been reported in the literature on many occasions. Most of the animals commonly involved are dogs, cats, cows, horses and camels. Injuries are usually on the trunk or limbs and sometimes on the face. Human injuries caused by an ostrich are rare and only three cases have been reported with severe ocular injury. To our knowledge, this is the first reported case of head injury caused by an ostrich in a child.


Microencapsulation of mammalian cells in a HEMA-MMA copolymer: effects on capsule morphology and permeability.
A new process for preparing uniform microcapsules with a hydroxyethyl methacrylate-methyl methacrylate copolymer (HEMA-MMA) has been devised. Capsule diameters were 900-1000 microns in diameter, (+/- 10-20 microns, +/- SD) depending on the precipitation conditions. The process involved the coextrusion of polymer solution (in PEG 200) and the mammalian cell suspension (here erythrocytes) through a needle assembly which is submerged in a layer of hexadecane which is in turn sitting above a stirred isotonic aqueous solution in a volumetric flask. The needle is repeatedly withdrawn from the hexadecane overlayer shearing a droplet from the needle tip which falls into the water, where the solvent is extracted to precipitate the polymer around the cells to yield the capsules. The morphology of the capsule wall was altered by changing the precipitation bath from phosphate buffered saline (PBS) to 0.3 M glycerol. This resulted in greater macroporosity in the wall, presumably because of the faster precipitation due to the higher solvent/precipitant compatibility with 0.3 M glycerol. The permeability to a series of test solutes (glucose, inulin, albumin, and alcohol dehydrogenase, ADH) increased by a factor of approximately 2, presumably because of the increased macroporosity. Addition of 15% water to the polymer solvent enhanced the macroporosity, presumably by bringing the system closer to the cloud point; however, there was no corresponding increase in permeability. There was a significant decrease in permeability between that of albumin (approximately 69,000 D) and ADH (approximately 150,000 D) suggesting that the molecular weight cut-off of these capsules was on the order of 100,000 D as desired. This process is now being evaluated for the encapsulation of pancreatic islets and other cells of potential clinical interest.


Sudden unilateral visual field loss.
We report a classical case of branch retinal artery occlusion (BRAO) in the acute setting and review the literature relating to the diagnostic, therapeutic and prognostic facets of this condition. BRAO can cause sudden visual loss and is not an infrequent presentation to emergency medical services. BRAO may indicate predisposing and related conditions capable of significant morbidity and mortality. Although current therapeutic practices in the acute setting are of uncertain benefit, conservative measures may be attempted in the emergency room by a nonophthalmologist with the aim of dislodging the causative embolus. Regardless of the current means of acute management, anitplatelet therapy and cardiovascular risk management remain the mainstay of treatment for BRAO. The potential for life-threatening systemic associations necessities investigation and multidisciplinary input.


Conformational difference in HMGB1 proteins of human neutrophils and lymphocytes revealed by epitope mapping of a monoclonal antibody.
HMGB1 and HMGB2 are abundant nonhistone chromosomal proteins in eukaryotic organisms. Their respective primary sequences are highly conserved. Our previous studies showed that these proteins are novel autoantigens of anti-neutrophil cytoplasmic antibodies in sera from patients with ulcerative colitis (UC), rheumatic disease and autoimmune hepatitis (AIH). In the present paper, we showed that anti-HMGB1 and HMGB2 antibodies in sera of patients with UC do not recognize HMGB1 in neutrophils while they recognize the protein in lymphocytes. Anti-HMGB2 monoclonal antibody FBH7, recognizing HMGB1 in lymphocytes, showed a similar profile to the antibodies in the patients' sera. In order to elucidate the difference in immunoreactivity to HMGB1 between neutrophils and lymphocytes, we mapped the epitope for FBH7 by means of several methods. The results showed that FBH7 recognizes the intact conformation composed of 52-56 residues of HMGB1 in lymphocytes. This suggested that HMGB1 in neutrophils is conformationally changed in the epitope or the peripheral structure of the epitope from the protein in lymphocytes. The apparent conformational change of HMGB1 between neutrophils and lymphocytes will be important for understanding the functional difference of HMGB1 in these cells.


Query Chem: a Google-powered web search combining text and chemical structures.
Query Chem (www.QueryChem.com) is a Web program that integrates chemical structure and text-based searching using publicly available chemical databases and Google's Web Application Program Interface (API). Query Chem makes it possible to search the Web for information about chemical structures without knowing their common names or identifiers. Furthermore, a structure can be combined with textual query terms to further restrict searches. Query Chem's search results can retrieve many interesting structure-property relationships of biomolecules on the Web.


Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging.
Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence.


[Effects of Recommended Consultation Practice Using Fracture Risk Assessment Tool and Fracture Evaluation Questionnaire for Early Detection of Osteoporosis at Community Pharmacies].
As one of the strategies for the early detection and treatment of osteoporosis, we have recommended visiting a hospital, based on the Fracture Risk Assessment Tool (FRAX®) and evaluation questionnaire for osteoporotic fracture risk. In this study, we evaluated the impact of intervention by community pharmacists by integrating our data for the FRAX® and questionnaire. The measurement of FRAX® and the questionnaire survey were conducted through participation in health seminars organized by a community general support center from June 2018 to December 2019. Participants with a FRAX® score more than 15% and at least one item in the questionnaire were considered to have "suspected osteoporosis" were recommended medical consultation. The medical treatment status for the participants considered to have "suspected osteoporosis" aged 40-90 years were analyzed. Of the 84 participants, 54 had a FRAX® score more than 15%, and 44 participants fulfilled at least one item in the questionnaire. Medical consultation was recommended to 26 of these 44 participants, excluding 18 under treatment. Of the 25 participants, six (excluding one who disagreed) received consultation, and medical treatment was started for four of them (66.7%). However, consultation with the attending physician was recommended to five of the 18 participants who were initially on treatment but discontinued it at the time of the survey. Consequently, two participants resumed their osteoporosis treatment. Our data suggest advantages of community pharmacists' intervention using FRAX® and a questionnaire for osteoporotic fracture risk measurement for early detection and medical treatment.


Cost of coronary heart disease in New Zealand.
To conservatively estimate the costs of coronary heart disease from the perspective of New Zealand society. A cross sectional or prevalence analysis (cases and associated costs in one year) was undertaken of the total annual cost of coronary heart disease. Estimates were made on an incremental basis of direct, indirect and intangible costs. Costs relate to 1989 volumes measured in March quarter 1992 dollars (net of goods and services tax). Cost estimates were in all instances conservative values. Direct medical costs amounted to $179 million and indirect costs were between $14 million and $24 million. Loss of life using the human capital approach ranged from $114 million to $264 million, but using the willingness to pay criteria, loss of life was $14,568 million. Because of the magnitude of the costs of coronary heart disease even small reductions in the incidence of coronary heart disease will produce substantial savings to society.


Ionizing radiation induces microhomology-mediated end joining in trans in yeast and mammalian cells.
DNA double-strand breaks repaired through nonhomologous end joining require no extended sequence homology as a template for the repair. A subset of end-joining events, termed microhomology-mediated end joining, occur between a few base pairs of homology, and such pathways have been implicated in different human cancers and genetic diseases. Here we investigated the effect of exposure of yeast and mammalian cells to ionizing radiation on the frequency and mechanism of rejoining of transfected unirradiated linear plasmid DNA. Cells were exposed to gamma radiation prior to plasmid transfection; subsequently the rejoined plasmids were recovered and the junction sequences were analyzed. In irradiated yeast cells, 68% of recovered plasmids contained microhomologies, compared to only 30% from unirradiated cells. Among them 57% of events used>or=4 bp of microhomology compared to only 11% from unirradiated cells. In irradiated mammalian cells, 54% of plasmids used>or=4 bp of microhomology compared to none from unirradiated cells. We conclude that exposure of yeast and mammalian cells to radiation prior to plasmid transfection enhances the frequency of microhomology-mediated end-joining events in trans. If such events occur within genomic locations, they may be involved in the generation of large deletions and other chromosomal aberrations that occur in cancer cells.


Collagen: an overview.
Collagen is a versatile material with biological properties that make it useful for the fabrication of implantable devices in medicine and dentistry. In this article we review collagen biosynthesis, structure, and types, as well as the properties that make it compatible with human tissues.


The sooner patients begin neurorehabilitation, the better their functional outcome.
To determine whether early neurorehabilitation improves a patient's functional recovery. A retrospective study was carried out on patients with severe traumatic brain injury (TBI) who underwent a minimum of 4 months of integral and multidisciplinary neurorehabilitation. Fifty-eight patients with severe TBI were assessed at admission and at discharge using the FIM + FAM scale. Two groups were formed based on time elapsed from brain injury to onset of rehabilitation. The early treatment group (ET) included patients who began rehabilitation within the first 9 months post-trauma; the late treatment group (LT) began after the 9-month cut-off date. Intra- and between-group analysis of FIM + FAM scores were carried out at admission and discharge. Multiple linear regression was used to determine the best predictors for functional rehabilitation. After neurorehabilitation, all subjects showed significant improvement in cognitive, motor, communication and psychosocial functioning. Moreover, the ET group showed better global functional outcome at discharge than patients who began later treatment. The best predictors for functional neurorehabilitation were months since injury, age, GCS score and months of treatment. It is concluded that the sooner patients begin neurorehabilitation, the better their functional outcome.


New insights into the biogenesis of human high-density lipoproteins.
The interest for the human HDL system was recently revived by the identification of the ABCA1 as a critical component in the formation and maintenance of plasma HDL levels. The present review focuses on recent progress in our understanding of the basic mechanisms underlying HDL biogenesis pathways. Several novel mechanisms governing ABCA1/apoA-I interactions have recently been identified: apolipoprotein A-I activates ABCA1 phosphorylation through the cAMP/protein kinase A-dependent pathway; the majority of ABCA1 exists as a tetramer in human living cell, supporting the concept that the homotetrameric ABCA1 complex constitutes the minimum functional unit for the formation of nascent HDL particles; apolipoprotein A-I has been shown to have a recycling retroendocytic pathway with uptake and resecretion of the lipidated nascent HDL particles by the cell, most likely through the ABCA1 transporter pathway; there is evidence that the speciation of nascent HDL into pre-beta and alpha-HDL is linked to specific cell lines, and occurs by both ABCA1-dependent and independent pathways. The fundamental mechanisms underlying the biogenesis, speciation and maturation of HDL remain complex and not well understood. Understanding the mechanisms governing HDL genesis at the cellular level could provide novel insights into the human atheroprotective system in health and disease.


Banana may be forbidden after endoscopic variceal ligation: a case report.
Acute variceal hemorrhage (AVH) is a devastating complication of liver cirrhosis. Endoscopic variceal ligation (EVL) is a useful endoscopic treatment for AVH with few complications. However, the issue regarding management of early re-bleeding after EVL still needs to be concerned. Furthermore, the dietary principle after EVL is unclear. There is no consensus regarding what food should be eaten after EVL. In this paper, we reported a patient who ate a banana after an EVL and then developed early re-bleeding episodes.


CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells.
Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE), a well-known active compound from bee propolis, has been previously identified as a strong antioxidant, anti-inflammatory, antiviral and anticancer molecule. In fact, CAPE is well documented as inducing cell death by inhibiting NFκB and by inducing pro-apoptotic pathways (i.e., p53). With the objective of developing stronger anticancer compounds, we studied 18 recently described CAPE derivatives for their ability to induce apoptosis in breast cancer cell lines. Five of the said compounds, including CAPE, were selected and subsequently characterised for their anticancer mechanism of action. We validated that CAPE is a potent inducer of caspase-dependent apoptosis. Interestingly, some newly synthesized CAPE derivatives also showed greater cell death activity than the lead CAPE structure. Similarly to CAPE, analog compounds elicited p53 activation. Interestingly, one compound in particular, analog 10, induced apoptosis in a p53-mutated cell line. These results suggest that our new CAPE analog compounds may display the capacity to induce breast cancer apoptosis in a p53-dependent and/or independent manner. These CAPE analogs could thus provide new therapeutic approaches for patients with varying genotypic signatures (such as p53 mutations) in a more specific and targeted fashion.


Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.
Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS). Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed. Somatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were PTEN and PIK3CA. PTEN was the most common in endometrioid histology, while PPP2R1A was the most commonly mutated gene in serous histology. The mutation rates of PPP2R1A and TP53 were significantly higher in advanced EC sample than in stage I samples (22.5% vs. 4.3% [p<0.001] and 8.4% vs. 1.4% [p=0.021], respectively). Survival analysis of the total population and endometrioid subgroup revealed that patients with PPP2R1A mutations had significantly shorter survival than did those without mutations (p=0.005 and p<0.001, respectively). PPP2R1A mutations might have a role in dismal prognosis of advanced EC.


Am I Really Bipolar? Personal Accounts of the Experience of Being Diagnosed With Bipolar II Disorder.
Bipolar disorder (BD) is a complex and chronic mental illness with highs and lows beyond the ordinary, which induces a significant risk of suicide. The aim of this study was to explore the experience of being diagnosed with BD and the impact that receiving a correct diagnosis had had on life situations and relationships with others. Semi-structured qualitative interviews were conducted with seven people diagnosed with BD. The results showed that the primary treatment all participants had received or were currently receiving was pharmacotherapy, typically without any psychological component. A major concern that arose was delayed diagnosis, leading to inadequate treatment, and lack of knowledge among professionals about non-typical forms of BD. Moreover, the experiences of others' reactions were multifold, though generally surprisingly positive. Generally, the participants had learned to recognize, understand and tackle early symptoms of both hypomanic and depressive episodes to avoid developing a full-blown acute episode. This study highlights the crucial importance of a collaborative relationship between the clinician and the patient.


Public Law 100-360, Medicare Catastrophic Coverage Act of 1988, 1 July 1988.
This Act significantly expands the US Medicare program of health care to the aged and disabled. Among the changes that it makes are the following: 1) eliminating the time limit on the number of days of inpatient hospital and hospice care covered; 2) increasing nursing home care to 150 days; 3) reducing deductibles and copayments for hospital and nursing home care; 4) establishing coverage for respite-care (up to 80 hours per year), mammography screening, and outpatient prescription drugs; and 5) lowering the income level below which persons must be covered by Medicaid. The Act also creates the US Bipartisan Commission on Comprehensive Health Care to examine issues related to comprehensive health care and comprehensive longterm health care for the aged and disabled. The changes in Medicaid are to be paid for by additional premiums on persons enrolled in Medicaid, determined in part by income level.


Activity of neurons in monkey superior colliculus during interrupted saccades.
1. Recent studies of the monkey superior colliculus (SC) have identified several types of cells in the intermediate layers (including burst, buildup, and fixation neurons) and the sequence of changes in their activity during the generation of saccadic eye movements. On the basis of these observations, several hypotheses about the organization of the SC leading to saccade generation have placed the SC in a feedback loop controlling the amplitude and direction of the impending saccade. We tested these hypotheses about the organization of the SC by perturbing the system while recording the activity of neurons within the SC. 2. We applied a brief high-frequency train of electrical stimulation among the fixation cells in the rostral pole of the SC. This momentarily interrupted the saccade in midflight: after the initial eye acceleration, the eye velocity decreased (frequently to 0) and then again accelerated. Despite the break in the saccade, these interrupted saccades were of about the same amplitude as normal saccades. The postinterruption saccades were usually initiated immediately after the termination of stimulation and occurred regardless of whether the saccade target was visible or not. The velocity-amplitude relationship of the preinterruption component of the saccade fell slightly above the main sequence for control saccades of that amplitude, whereas postinterruption saccades fell near the main sequence. 3. Collicular burst neurons are silent during fixation and discharge a robust burst of action potentials for saccades to a restricted region of the visual field that define a closed movement field. During the stimulation-induced saccadic interruption, these burst neurons all showed a pause in their high-frequency discharge. During an interrupted saccade to a visual target, the typical saccade-related burst was broken into two parts: the first part of the burst began before the initial preinterruption saccade; the second burst began before the postinterruption saccade. 4. We quantified three aspects of the resumption of activity of burst neurons following saccade interruption: 1) the total number of spikes in the pre- and postinterruption bursts, was very similar to the total number of spikes in the control saccade burst; 2) the increase in total duration of the burst (preinterruption period + interruption + postinterruption period) was highly correlated with the increase in total saccade duration (preinterruption saccade + interruption + postinterruption saccade); and 3) the time course of the postinterruption saccade and the resumed cell discharge both followed the same monotonic trajectory as the control saccade in most cells. 5. The same population of burst neurons was active for both the preinterruption and the postinterruption saccades, provided that the stimulation was brief enough to allow the postinterruption saccade to occur immediately. If the postinterruption saccade was delayed by > 100 ms, then burst neurons at a new and more rostral locus related to such smaller saccades became active in association with the smaller remaining saccade. We interpret this shift in active locations within the SC as a termination of the initial saccadic error command and the triggering of a new one. 6. Buildup neurons usually had two aspects to their discharge: a high-frequency burst for saccades of the optimal amplitude and direction (similar to burst neurons), and a low-frequency discharge for saccades of optimal direction whose amplitudes were equal to or greater than the optimal (different from burst neurons). The stimulation-induced interruption in saccade trajectory differentially affected these two components of buildup neuron discharge. The high-frequency burst component was affected in a manner very similar to the burst neurons.(ABSTRACT TRUNCATED)


IFNAR1 Degradation: A New Mechanism for Tumor Immune Evasion?
Type I interferons have been shown to play a major role in anti-cancer immunity. In this issue of Cancer Cell, Katlinski et al. describe tumor-induced degradation of type I interferon receptor IFNAR1 chain as a new immune-evasion mechanism in colorectal cancers. Stabilizing IFNAR1 inhibits tumor growth and improves immunotherapy efficacy.


Surface Electrocardiographic Parameters of Children and Adolescents Diagnosed with Attention-Deficit/Hyperactivity Disorder in an Ambulatory Community Pediatric Center: A Focus on Cardiac Repolarization Electrocardiogram Intervals.
Objectives: Our research aims were to determine if repolarization measures (QTcF, QTcB, JTcF, and JTcB) in attention-deficit/hyperactivity disorder (ADHD) children and adolescents differ from normal subjects and determine if the JTc interval duration, as a purer repolarization measure than QTc, strengthens the differentiation between ADHD and normal children and adolescents. Methods: This study included 418 subjects aged 5-18 years who were diagnosed with ADHD, and 1948 subjects in a historical normal control group. One-way analysis of variance (ANOVA) was performed to compare the independent groups on normal continuous outcomes. Means and standard deviations (SDs) were reported and interpreted for the ANOVA. Logistic regression analysis was performed to test the ability of four variables (QTcB, QTcF, JTcB, and JTcF) to predict an ADHD diagnosis, with age and gender as independent covariates. The log odds with standard errors for each variable were reported and interpreted for the logistic models. Results: In the nominal logistic regressions with JTcF ≥322 or JTcB ≥335 (values 1 SD above the mean of the control group), age and sex were significant contributors to the models that showed that subjects with a JTcF ≥322 ms had a statistically and significantly higher probability to be diagnosed with ADHD in comparison with normal control subjects (odds ratio [OR]: 2.6, 95% confidence interval [95% CI] 2.02-3.33, p < 0.0001). Similarly, those subjects with a JTcB ≥335 ms were 2.7 times more likely to be diagnosed with ADHD than normal control subjects (OR: 2.7, 95% CI 2.1-3.45, p < 0.0001). Conclusions: JTc provided a clearer separation of the groups than QTc. JTcB and JTcF 1 SD above the control group means are strong predictors of ADHD diagnosis and remain so even when strong demographic predictors of longer QTc (age and sex) are included in the regression models. Consideration should be given to recording a pretreatment electrocardiogram in all children and adolescents with ADHD, and to measuring and monitoring JTc in patients with ADHD, especially when considering the addition of QT prolonging drugs.


A role of the mitotic spindle checkpoint in the cellular response to DNA replication stress.
Replication stress is a frequent and early event during tumorigenesis. Whereas the cellular responses to a persistent block of replication fork progression have been extensively studied, relatively little is known about how cells respond to low-intensity replication stress. However, transient replication fork perturbations are likely to occur even more frequently in tumor cells than a permanent replication arrest. We report here that transient, low intensity replication stress leads to a rapid activation of the DNA replication checkpoint but to a significantly delayed apoptotic response in a small but significant number of cells. This late apoptotic response was independent of p53 and we found evidence for cell death during mitosis in a proportion of cells. To further explore the role of p53 in the response to replication stress, we analyzed mouse embryonic fibroblasts (MEFs) deficient of p53 in comparison to wild-type or p63- or p73-deficient MEFs. We detected a significant increase of apoptosis and morphological signs of failed mitosis such as multinucleation in p53-deficient MEFs following replication stress, but not in wild-type or p63- or p73-deficient cells. Multinucleated p53-deficient MEFs frequently retained cyclin B1 expression indicating a persistently activated mitotic spindle checkpoint. Collectively, our results suggest that the cellular response to replication stress involves the mitotic spindle checkpoint in a proportion of cells. These findings imply that the mitotic spindle checkpoint may act in concert with DNA damage and cell-cycle checkpoints as an early anti-tumor barrier and provide a possible explanation for its frequent relaxation in human cancer.


Performance of chemical shift-based water-fat separation with self-calibrated fat spectrum is sensitive to echo times.
Chemical shift-based water-fat separation method utilises water-fat resonance frequency difference to decompose signals into water and fat partitions in magnetic resonance imaging (MRI) on a pixel-wise basis. It provides an effective way to measure fat fraction, or to suppress fat signal which might obscure underlying pathology. IDEAL (Iterative decomposition of water and fat with echo asymmetry and least-squares estimation) algorithm with multi-peak fat spectral modelling has been developed. Recent studies have discussed the performance of this algorithm assuming that the frequencies and relative amplitudes of fat peaks are constant among all subjects. However, the fat spectra vary in different tissues, thus a self-calibration method which estimates the fat spectrum directly from the data provides more accurate results. In this work, we analyse the performance of multi-peak IDEAL algorithm with self-calibrated fat spectrum by theoretical calculation, simulation, and experiments, and find optimal echo time increments which provide reliable water-fat separation.


Tumor cell adhesion to endothelial cells: endothelial leukocyte adhesion molecule-1 as an inducible adhesive receptor specific for colon carcinoma cells.
Activation of endothelial cells by the two inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor strongly increases tumor cell adhesion. We describe antibody inhibition studies showing that the endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell-surface glycoprotein selectively expressed by cytokine-activated endothelial cells and responsible for neutrophil adhesion, is the major, if not the only, mediator of colon carcinoma cell adhesion to activated endothelial cells. Among the different tumor cell lines tested, seven colon carcinoma cell lines were sensitive to ELAM-1 antibodies. Adhesion of melanoma, osteosarcoma, and lung, cervix, or kidney carcinoma cell lines to IL-1-treated endothelial cells was not affected by the ELAM-1 antibody. This result suggests that ELAM-1 is selectively recognized by colon carcinoma cells and that adhesion of tumor cells to activated endothelial cells could be mediated by different and specific mechanisms.


Frequency of the delta F508 mutation on cystic fibrosis chromosomes in Denmark.
We have investigated the frequency of the delta F508 mutation on cystic fibrosis (CF) chromosomes in Denmark. Of 304 chromosome tested, 86.8% have the delta F508 mutation. The majority of the chromosomes with this mutation are found on chromosomes with the XV2c/KM19 haplotype B (97.3%), whereas 15/16 chromosomes with haplotype C have another mutation, confirming that only very few mutations will account for the majority of CF genes in the Danish population.


The evolutionary radiation of diverse osmotolerant physiologies in killifish (Fundulus sp.).
Fish have radiated to exploit diverse habitats, but little is known about the evolutionary lability and directionality of associated physiological specialization. Killifish of the genus Fundulus present a compelling system to explore the evolution of osmotic tolerance because closely related species have evolved to occupy most osmotic niches, and physiological osmotic tolerance data are available for most species. This study seeks to determine the number of times, and the rate at which, alternate osmotic tolerance physiologies have evolved, and to determine the directionality of physiological transitions, by mapping comparative physiology data to a molecular phylogeny for the genus. Character mapping and phylogeographic inference indicate that freshwater tolerance is derived, can evolve rapidly, has evolved several times within the genus, and that variation in osmotic tolerance contributes to defining species distributions. The derivation of alternate physiologies within Fundulus appears associated with contraction of physiological plasticity rather than shifts in tolerance ranges, and the degree of contraction is surprisingly similar across convergent physiological types. The rate of physiological transition is relatively high within Fundulus compared to other taxa, but directionality from high salt tolerance to intolerance appears to be the rule. Together, these comparative physiology and phylogenetic data yield insight into the patterns of evolution of ecological specialization.


Determining the requirements for cooperative DNA binding by Swi5p and Pho2p (Grf10p/Bas2p) at the HO promoter.
SW15 encodes a zinc finger DNA binding protein required for the transcription of the Saccharomyces cerevisiae HO gene, and PHO2 encodes a homeodomain DNA binding protein. In vitro biochemical studies using purified Swi5p and Pho2p proteins have demonstrated that Swi5p and Pho2p bind cooperatively to the HO promoter. In this report we investigate the regions of the Swi5p and Pho2p proteins required for cooperative DNA binding. The analysis of each protein gives a similar result: the zinc finger or homeodomain DNA binding domains are each sufficient for in vitro DNA binding, but additional regions of each protein are required for cooperative DNA binding. In vitro and in vivo experiments were conducted with promoters with altered spacing between the Pho2p and Swi5p binding sites. Mutations that increased the distance between the two binding sites had minimal effects on either in vitro cooperative DNA binding or in vivo upstream activating sequence activity. These observations suggest that the interaction domains of Swi5p and Pho2p are flexible and can tolerate an increase in distance between the two binding sites. The mechanism of the cooperative DNA binding by Swi5p and Pho2p is discussed.


N-acetylaspartate concentration in corpus callosum is positively correlated with intelligence in adolescents.
The corpus callosum is the largest white matter bundle in the brain and integrates inter-hemispheric cortices during sensory-motor and high-order cognitive processes. The aim of the present study was to investigate the associations between the metabolite concentrations in the corpus callosum and intelligence among adolescents. Thirty male adolescents aged between 14 and 16 years were included into the study. We measured the intelligence quotient (IQ) scores of the subjects by using the Wechsler Intelligence Scale for Children-Revised (verbal, performance and full-scale IQ) test. We used proton MR spectroscopy to measure the absolute concentrations of N-acetylasparate (NAA), creatine (Cr) and choline (Cho) in the genu, midbody and isthmus/splenium regions of the corpus callosum. We also measured the whole brain parenchymal size and used it as a confounding factor in the statistical analyses. We assessed the correlations between neurometabolite concentrations and verbal, performance and full-scale IQ scores. We found a significant positive correlation between the whole brain parenchymal size and the full-scale IQ scores. And, the NAA concentration in the isthmus/splenium region was positively correlated with the performance IQ and full-scale IQ scores. NAA is a marker of neuro/axonal integrity. NAA concentration in white matter is related to the structural and functional integrity of axonal fibers. The positive correlation of the IQ scores with the NAA concentrations in the isthmus/splenium region indicates that more efficient inter-hemispheric data transfer between parieto-occipital cortices may enhance intellectual performance.


Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells.
Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling. Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and in rodent breast cancer models. Despite the suggested linkage between obesity and breast cancer, the local influence of bioactive dietary components on mammary adiposity for antitumor effects remains unknown. Herein, we report that post-weaning dietary exposure to soy protein isolate and its bioactive isoflavone genistein (GEN) lowered mammary adiposity and increased mammary tumor suppressor PTEN and E-cadherin expression in female mice, relative to control casein diet. To ascertain GEN's role in mammary adipose deposition that may affect underlying epithelial cell phenotype, we evaluated GEN's effects on SV40-immortalized mouse mammary stromal fibroblast-like (MSF) cells during differentiation into adipocytes. MSF cells cultured in a differentiation medium with 40 nM GEN showed reductions in mature adipocyte numbers, triglyceride accumulation, and Pparγ (Pparg) and fatty acid synthase transcript levels. GEN inhibition of adipose differentiation was accompanied by increased estrogen receptor β (Erβ (Esr2)) gene expression and was modestly recapitulated by ERβ-selective agonist 2,3-bis-(4-hydroxyphenyl)-propionitrile (DPN). Reduction of Erβ expression by siRNA targeting increased Pparγ transcript levels and stromal fibroblast differentiation into mature adipocytes; the latter was reversed by GEN but not by DPN. Conditioned medium from GEN-treated adipocytes diminished anchorage-independent mammosphere formation of human MCF-7 breast cancer cells. Our results suggest a mechanistic pathway to support direct regulation of mammary adiposity by GEN for breast cancer prevention.


Delayed diagnosis of oral cancer in Iran: challenge for prevention.
The aim of this study was to investigate the diagnostic delay and its determinants among oral cancer patients in Tehran, Iran. This study was conducted between September 2004 and September 2006 in three university hospitals, and included 100 consecutive patients with primary oral squamous cell carcinoma (international classification of disease, ICD-10 sites C01 to C06). Data were obtained through questionnaire interviews and medical records of the patients were reviewed to obtain information on the date of diagnosis, primary tumour site and the stage of the tumour at the time of diagnosis. Statistical analysis was performed by t test, ANOVA and logistic regression. The mean diagnostic delay was 7.2 months (SD 7.5, range 1 to 36 and median 4). The most important determinants of longer diagnostic delay were being single (OR = 4.8; 95% CI = 1.5 to 14.8; P < 0.05) and being at advanced tumour stages (OR = 5.3; 95% CI = 1.8 to 15.6; P < 0.01). The mean patient and professional delays were 5.3 months (SD 6.1 and median 2) and 2.1 months (SD 2.1 and median 1), respectively. Patients at advanced tumour stages were more likely to have longer patient and professional delays than those at early stages (OR = 5.6; 95% CI = 1.8 to 17.3 and OR = 3.4; 95% CI = 1.2 to 9.4, respectively; P < 0.05). Living alone was also a determinant of longer patient and professional delays (OR = 7.1; 95% CI = 2.0 to 24.7, OR = 3.5; 95% CI = 1.2 to 10.3, respectively; P < 0.05). Developing preventive programmes that focus on the enhancement of public and professional awareness about oral cancer is essential to promote earlier diagnosis in Iran.


Expert opinions on nutrition issues in clinical dentistry.
Diet assessment and counseling are essential components of comprehensive preventive dental care programs. However, the lack of consensus on what constitutes appropriate nutrition services has resulted in diversity in the level and quality of such services to dental patients. Seventy nine nationally recognized experts in dental nutrition were surveyed using the Delphi method to seek consensus on the appropriate scope of nutrition in clinical dentistry.


Role of sociocultural factors in hepatitis B screening among Asian Americans.
To apply the proposed Sociocultural Health Behavior Model to determine association of factors related to hepatitis B virus (HBV) screening among Asian Americans. A cross-sectional design of 1312 Asian men and women 18 years and older. The frequency distribution analysis and chi square analysis were used for the initial screening of the following variables: access/satisfaction with health care, enabling, predisposing, cultural, and health belief factors. Univariate and multivariate analyses were conducted on factors for HBV screening using logistic regression analysis. Correlates to HBV screening included demographics, cultural factors, enabling factors, and family/social support factors. Enabling factors were more likely to be associated with HBV screening. The model highlights the role sociocultural factors play in HBV screening. Findings reinforce the need for HBV screening programs and indicate programs could be more effective if they included these components and were sensitive to ethnic and cultural factors.


RhoA regulates calcium-independent periodic contractions of the cell cortex.
When microtubules are depolymerized in spreading cells, they experience morphological oscillations characterized by a period of about a minute, indicating that normal interactions between the microfilament and microtubule systems have been significantly altered. This experimental system provides a test bed for the development of both fine- and coarse-grained models of complex motile processes, but such models need to be adequately informed by experiment. Using criteria based on Fourier transform analysis, we detect spontaneous oscillations in spreading cells. However, their amplitude and tendency to operate at a single frequency are greatly enhanced by microtubule depolymerization. Knockdown of RhoA and addition of various inhibitors of the downstream effector of RhoA, Rho kinase, block oscillatory behavior. Inhibiting calcium fluxes from endoplasmic reticulum stores and from the extracellular medium does not significantly affect the ability of cells to oscillate, indicating that calcium plays a subordinate regulatory role compared to Rho. We characterized the dynamic structure of the oscillating cell by light, fluorescence, and electron microscopy, showing how oscillating cells are dynamically polarized in terms of their overall morphology, f-actin and phosphorylated myosin light chain distribution, and nuclear position and shape. Not only will these studies guide future experiments, they will also provide a framework for the development of refined mathematical models of the oscillatory process.


Seroprevalence and Determinants of ToRCH Pathogens in Pregnant Women in the Sub-Himalayan Region.
Introduction Toxoplasma gondii (TG), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus type 1 and 2 (HSV 1 and 2) cause mild maternal morbidity but have serious fetal consequences. The prevalence of these infections varies widely by country and population subgroup, and the paucity of data from the hilly state of Uttarakhand prompted us to undertake this study on their seroprevalence and association with potential risk factors. Methods Serum samples received from pregnant women attending the antenatal clinic of All India Institute of Medical Sciences, Rishikesh, between January 2016 to December 2019 were tested for TG-, RV-, CMV, and HSV-specific IgM and IgG by capture enzyme-linked immunoassay (ELISA). The data were then analyzed to determine the seroprevalence of the major ToRCH infections (toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus, and herpes), and Fisher's exact test was applied to check association with potential risk factors. Results Out of 165 pregnant women who were screened for the four major ToRCH pathogens, overall seroprevalence was 41.2% for TG (IgM=13.3%; IgG=38.2%), 80.0% for RV (IgM=3.0%; IgG=80.0%), 61.8% for CMV (IgM=1.8%; IgG=61.8%), and 42.4% for HSV (IgM=4.3%; IgG=40.6). TG was significantly associated with increasing maternal age (p-value=0.007). The seropositivity of RV was maximum in the drier and windy months of January-March (p-value=0.004), while that of TG in the warmer months of April-June (p-value=0.03). HSV prevalence was comparatively more common in Muslim women (p-value=0.05). Women presenting with bad obstetric history (BOH) and multiparous women were at higher risk for TG-RV-HSV and TG-RV-CMV, respectively. Conclusion Considering the high prevalence and risk of ToRCH infections in this region, we suggest disease-specific screening based on maternal history. Recognition of the burden of ToRCH infections in pregnant women is vital in clinicians' decisions and implementing control measures.


A molecular dynamics study of the inclusion of mono- and disubstituted benzenes in beta-cyclodextrin.
The interaction between beta-cyclodextrin and five mono- and disubstituted benzenes in water was investigated by means of molecular dynamics. The trajectories were calculated for each system, imposing a 1:1 host-guest stoichiometry with 512 water molecules. Periodic boundary conditions were adopted. The results account for the formation of stable adducts and the predicted geometry agrees with experimental circular dichroism data.


Fruit dry matter concentration: a new quality metric for apples.
In the fresh apple market fruit must be crisp and juicy to attract buyers to purchase again. However, recent studies have shown that consumer acceptability could be further enhanced by improving taste. This study evaluates the use of fruit dry matter concentration (DMC) as a new fruit quality metric for apple. Fruit samples collected at harvest, in the two main fruit growing regions of New Zealand, showed a variation in mean fruit DMC from 130 to 156 g kg(-1) with 'Royal Gala' and with 'Scifresh' from 152 to 176 g kg(-1). Individual fruit DMC showed a larger range, from 108 to 189 g kg(-1) with 'Royal Gala' and from 125 to 201 g kg(-1) with 'Scifresh'. Fruit DMC proved a more reliable predictor of total soluble solids after 12 weeks of air storage at 0.5 °C than TSS at harvest for both 'Royal Gala' and 'Scifresh'. Fruit DMC was also positively related to flesh firmness, although this relationship was not as strong as that seen with soluble solids and was more dependent on cultivar. Consumer studies showed that consumer preference was positively related to fruit DMC of 'Royal Gala' apples. Fruit DMC can therefore be measured before or at harvest, and be used to predict the sensory potential for the fruit after storage.


Stable isotope aided evaluation of community nutrition program: effect of food supplementation schemes on maternal and infant nutritional status.
The supplementation program of the community nutrition project (PNC) launched by the Senegalese Government in order to protect the most vulnerable groups (children and women) was evaluated. Using a stable isotope (deuterium), we assessed the effect of the PNC on breastmilk output, mother's body composition, and baby's growth at three months of lactation. Breastmilk triglycerides, lactose, protein, and zinc were also determined. Mothers who were supplemented more than 60 days during pregnancy showed a significant increase in fat-free mass as compared to those who were supplemented for less than 30 days (p = .03). Breastmilk output was not influenced by the supplementation, but breastmilk lactose, total protein, and zinc contents increased significantly (p < .01) in the supplemented mothers. Growth of the babies of the supplemented mothers was better than that of those whose mothers were not supplemented. It was concluded that the food supplementation had beneficial effects on both mothers' and babies' nutritional status depending on the onset of the supplementation.


Overcoming perspective elongation effects in laser-guide-star-aided adaptive optics.
Tracking the instantaneous position of the laser guide star removes its perspective elongation thus allowing an increased separation of the laser transmitter from its telescope.


Z-ring-independent interaction between a subdomain of FtsA and late septation proteins as revealed by a polar recruitment assay.
FtsA, a member of the ATPase superfamily that includes actin and bacterial actin homologs, is essential for cell division of Escherichia coli and is recruited to the Z ring. In turn, recruitment of later essential division proteins to the Z ring is dependent on FtsA. In a polar recruitment assay, we found that FtsA can recruit at least two late proteins, FtsI and FtsN, to the cell poles independently of Z rings. Moreover, a unique structural domain of FtsA, subdomain 1c, which is divergent in the other ATPase superfamily members, is sufficient for this recruitment but not required for the ability of FtsA to localize to Z rings. Surprisingly, targeting the 1c subdomain to the Z ring by fusing it to FtsZ could partially suppress a thermosensitive ftsA mutation. These results suggest that subdomain 1c of FtsA is a completely independent functional domain with an important role in interacting with a septation protein subassembly.


Rare case of extra-peritoneal brown fat (hibernoma) mimicking dumbbell-shaped liposarcoma.
Hibernomas are a very rare and benign soft tissue tumour that originate from brown adipose tissue. While they are not histologically malignant, they may be indistinguishable from aggressive tumours such as liposarcomas on imaging. It is, therefore, important to consider it as a differential diagnosis when a suspicious fatty lesion is seen on imaging. This may prevent unnecessary invasive surgery and patient stress. This paper illustrates the clinical presentation, radiological features, and histological diagnosis of a patient with a rare dumbbell-shaped hibernoma in the pelvis.


A review of China's national policies to strengthen primary care 2003-2018.
The Chinese government has been prioritising the strengthening of its primary care system over the past two decades. This study reviews China's national policies in this domain from 2003 to 2018, incorporating academic literature and interviews with health officials and primary care providers. The aim is to assess these policies in alignment with the government's reform agenda and the ideal primary care system advocated in the public health literature. Initially focusing on network and infrastructure development, the Chinese government has progressively shifted its focus towards enhancing human resources and improving the service attributes of primary care facilities. Supported by detailed guidelines and increased funding, substantial progress has been made. Despite these advancements, significant gaps persist when comparing the current state of China's primary care system to the envisioned ideal. To gain a comprehensive understanding of these gaps, it is crucial to consider the Chinese government's agenda and the country's unique development trajectory, which has been influenced by its history of planned economy.


Stereocalpin A inhibits the expression of adhesion molecules in activated vascular smooth muscle cells.
Up-regulation of cell adhesion molecules on vascular smooth muscle cells (VSMCs) and leukocyte recruitment to the vascular wall contribute to vascular inflammation and atherosclerosis. Stereocalpin A, a chemical compound of the Antarctic lichen Ramalina terebarata, displays tumoricidal activity against several different tumor cell types. However, other biological activities of stereocalpin A and its molecular mechanisms remain unknown. In this study, our work is directed toward studying the in vitro effects of stereocalpin A on the ability to suppress the expression of adhesion molecules induced by TNF-α in vascular smooth muscle cells. Pretreatment of VSMCs for 2h with stereocalpin A at nontoxic concentrations of 0.1-10 μg/ml inhibited TNF-α-induced adhesion of THP-1 monocytic cells and expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Stereocalpin A reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Stereocalpin A also inhibited NK-κB activation induced by TNF-α. Moreover, stereocalpin A inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα, and nuclear translocation of NF-κB. Hence, we describe a new anti-inflammatory activity and mechanism of stereocalpin A, owing to the negative regulation of TNF-α-induced adhesion molecule and MCP-1 expression, monocyte adhesion and ROS production in vascular smooth muscle cells. These results suggest that stereocalpin A has the potential to exert a protective effect by modulating inflammation within the atherosclerotic lesion.


Midwives call for more support in safe motherhood.
Midwives need more backing to help them carry out their roles effectively. Midwives at an international workshop in May called for midwifery practice to be evaluated and improved so as to better achieve the goals of safe motherhood. The workshop on "Midwifery Practice--Measuring, Developing and Mobilizing Quality of Care" was the third in a series of workshops run jointly by the International Confederation of Midwives (ICM), the United Nations Children's Fund (UNICEF) and WHO. 41 midwives from 27 countries with high maternal mortality attended the workshop in Vancouver, Canada, on 7-8 May just prior to the ICM congress. Participants exchanged ideas on how midwives themselves can take responsibility for assessing and promoting high standards of maternity care. Plenary sessions and group work gave midwives the chance to learn how to determine what constitutes quality midwifery care. At the end of the workshop midwives drew up individual action plans to implement when they got back to their own countries. Workshop participants agreed an action statement addressed to ICM, WHO, UNICEF and to midwives themselves.


Microbial community shifts reflect losses of native soil carbon with pyrogenic and fresh organic matter additions and are greatest in low-carbon soils.
Soil organic carbon (SOC) plays an important role in regulating global climate change, carbon and nutrient cycling in soils, and soil moisture. Organic matter (OM) additions to soils can affect the rate at which SOC is mineralized by microbes, with potentially important effects on SOC stocks. Understanding how pyrogenic organic matter (PyOM) affects the cycling of native SOC (nSOC) and the soil microbes responsible for these effects is important for fire-affected ecosystems as well as for biochar-amended systems. We used an incubation trial with five different soils from National Ecological Observatory Network sites across the US and 13C-labelled 350°C corn stover PyOM and fresh corn stover OM to trace nSOC-derived CO2 emissions with and without PyOM and OM amendments. We used high-throughput sequencing of rRNA genes to characterize bacterial, archaeal, and fungal communities and their response to PyOM and OM in soils that were previously stored at -80°C. We found that the effects of amendments on nSOC-derived CO2 reflected the unamended soil C status, where relative increases in C mineralization were greatest in low-C soils. OM additions produced much greater effects on nSOC-CO2 emissions than PyOM additions. Furthermore, the magnitude of microbial community composition change mirrored the magnitude of increases in nSOC-CO2, indicating a specific subset of microbes were likely responsible for the observed changes in nSOC mineralization. However, PyOM responders differed across soils and did not necessarily reflect a common "charosphere". Overall, this study suggests that soils that already have low SOC may be particularly vulnerable to short-term increases in SOC loss with OM or PyOM additions.Importance Soil organic matter (SOM) has an important role in global climate change, carbon and nutrient cycling in soils, and soil moisture dynamics. Understanding the processes that affect SOM stocks is important for managing these functions. Recently, understanding how fire-affected organic matter (or "pyrogenic" organic matter (PyOM)) affects existing SOM stocks has become increasingly important, both due to changing fire regimes, and to interest in "biochar" - pyrogenic organic matter that is produced intentionally for carbon management or as an agricultural soil amendment. We found that soils with less SOM were more prone to increased losses with PyOM (and fresh organic matter) additions, and that soil microbial communities changed more in soils that also had greater SOM losses with PyOM additions. This suggests that soils that already have low SOM content may be particularly vulnerable to short-term increases in SOM loss, and that a subset of the soil microbial community is likely responsible for these effects.


Rising oceans, flooded towns: How Georgia coastline communities are readying to recover despite a changing climate.
Climate change is posing a significant threat to the coastal counties of Georgia. The Georgia Department of Natural Resources and Hagerty Consulting have recognised this threat and are facilitating a nine-year project aimed at developing a disaster recovery and redevelopment plan for the state's coastal communities, and providing state-wide technical assistance. This paper provides an overview of this planning initiative and summarises the many insights into the pre-disaster recovery and resilience planning process gained from this project.


Dynamic simulations of adhesion and friction in chemical force microscopy.
A hybrid molecular simulation approach has been applied to investigate dynamic adhesion and friction between a chemical force microscope (CFM) tip and a substrate, both modified by self-assembled monolayers (SAMs) with hydrophobic methyl (CH(3)) or hydrophilic hydroxyl (OH) terminal groups. The method combines a dynamic model for the CFM tip-cantilever system and a molecular dynamics (MD) relaxation technique for SAMs on Au(111) at room temperature. The hybrid simulation method allows one to simulate force-distance curves (or adhesion) and friction loops (or friction coefficient) in the CFM on the experimental time scale for the first time. The simulation results also provide valuable molecular information at the interface that is not accessible in CFM experiments, such as the actual tip position with respect to the cantilever support position, molecular and hydrogen-bonding structures at the interface, and load distributions among different molecular chains (or single-molecule forces). Results show that the adhesion force and friction coefficient for the OH/OH contact pair are much larger than those for the CH(3)/CH(3) pair due to the formation of hydrogen bonds. During the retraction of a CFM tip from a surface, the CFM tip is away from the sample surface slightly while the spring undergoes dramatic elongation in the normal direction before rupture occurs. Single-molecule forces are distributed unevenly at the contact area. Surface energies calculated for functionalized surfaces compare well with those determined by experiments.


ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle.
In this study, we aimed to directly quantify the relative contribution of Ca(2+) cycling to resting metabolic rate in mouse fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) skeletal muscle. Resting oxygen consumption of isolated muscles (Vo(2), microl.g wet wt(-1).s(-1)) measured polarographically at 30 degrees C was approximately 25% higher in soleus (0.61 +/- .03) than in EDL (0.46 +/- .03). To quantify the specific contribution of Ca(2+) cycling to resting metabolic rate, cyclopiazonic acid (CPA), a highly specific inhibitor of sarco(endo)plasmic reticulum Ca(2+) ATPases (SERCAs), was added to the bath at different concentrations (1, 5, 10, and 15 microM). There was a concentration-dependent effect of CPA on Vo(2), with increasing CPA concentrations up to 10 microM resulting in progressively greater reductions in muscle Vo(2). There were no differences between 10 and 15 microM CPA, indicating that 10 microM CPA induces maximal inhibition of SERCAs in isolated muscle preparations. Relative reduction in muscle Vo(2) in response to CPA was nearly identical in EDL (1 microM, 10.6 +/- 3.0%; 5 microM, 33.2 +/- 3.4%; 10 microM, 49.2 +/- 2.9%; 15 microM, 50.9 +/- 2.1%) and soleus (1 microM, 11.2 +/- 1.5%; 5 microM, 37.7 +/- 2.4%; 10 microM, 50.0 +/- 1.3%; 15 microM, 49.9 +/- 1.6%). The results indicate that ATP consumption by SERCAs is responsible for approximately 50% of resting metabolic rate in both mouse fast- and slow-twitch muscles at 30 degrees C. Thus SERCA pumps in skeletal muscle could represent an important control point for energy balance regulation and a potential target for metabolic alterations to oppose obesity.


Hedgehog signaling is required for the maintenance of mesenchymal nephron progenitors.
Mesenchymal nephron progenitors (mNPs) give rise to all nephron tubules in the mammalian kidney. Since premature depletion of these cells leads to low nephron numbers, high blood pressure, and various renal diseases, it is critical to understand how mNPs are maintained. While Fgf, Bmp, and Wnt signaling pathways are known to be required for the maintenance of these cells, it is unclear if any other signaling pathways also play roles. To test the potential role of Hedgehog signaling in mNPs, we conditionally deleted Shh from the collecting duct and Smo from the nephron lineage. To identify the genes regulated by Hedgehog signaling in mNPs, we performed RNA-seq analysis from mNPs with different Smo doses. To test if the upregulation of Notch signaling mimics loss of Hedgehog signaling, we performed Jag1 gain-of-function study in mNPs. We found that loss of either Shh or Smo resulted in premature depletion of mNPs. Our transcriptional profiling data from Smo loss- and gain-of-function mutant mNPs suggested that Hedgehog signaling inhibited the activation of Notch signaling and upregulated the expression of Fox transcription factors such as Foxc1 and Foxp4. Consistent with these observations, we found that ectopic expression of Jag1 caused the premature depletion of mNPs as seen in the Smo mutant kidney. We also found that Foxc1 was capable of binding to mitotic condensed chromatin, a hallmark of a pioneer factor. Our study demonstrates a previously unappreciated role of Hedgehog signaling in preventing premature depletion of mNPs by repressing Notch signaling and likely by activating the expression of pioneer factors.


Effect of gefitinib on serum EGFR and CYFRA21-1 in patients with advanced non-small cell lung cancer.
Changes of epidermal growth factor receptor (EGFR) and cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with advanced non-small cell lung cancer (NSCLC) before and after gefitinib treatment were observed to explore the significance of such changes. A total of 175 patients with advanced NSCLC who were admitted to Hubei Cancer Hospital from July 2012 to October 2015 were collected and divided into two groups: the control group (85 patients who received conventional chemotherapy) and the experimental group (90 patients treated with gefitinib combined with chemotherapy). The serum expression levels of EGFR and CYFRA21-1 were detected by enzyme-linked immunosorbent assay (ELISA). The therapeutic efficacy and 3-year survival of the two groups were compared, and the factors affecting the survival of the patients were analyzed. The total effective rate and local effective rate of the experimental group were significantly higher than those of the control group (P<0.05). Before treatment, no significant difference was detected in the levels of EGFR and CYFRA21-1 between the two groups (P>0.05). After treatment, the expression levels of EGFR and CYFRA21-1 in the two groups were significantly lower than those before treatment (P<0.05). According to the 3-year survival rate, the experimental group was divided into the survival group and the non-survival group. Single factor analysis was performed on the general data, showing that the influencing factors of the survival include the KPS score, smoking history, number of lesions, pathological stage, EGFR, and CYFRA21-1. Gefitinib can bring significantly improved therapeutic efficacy, lower expression levels of EGFR and CYFRA21-1, and longer survival time for patients with advanced NSCLC. Indicators including confirmed smoking history, a KPS score less than or equal to 60 points, multiple lesions, pathological stage IV, high expression of EGFR and CYFRA21-1, are important factors affecting the survival of patient with advanced NSCLC.


Neuropsychologic test performance in amateur boxers.
Cognitive functions of 23 amateur boxers were assessed immediately before and after an amateur boxing event. A range of cognitive measures were employed including tasks of verbal, figural, and incidental memory, motor functions, attention and concentration, and information processing speed. Compared to their prefight performance, boxers demonstrated impairments in verbal and incidental memory, but enhanced executive and motor functions postfight. There were no observed differences between winners and losers on any of the measures. The results are compared to other studies that have shown only minor changes in cognitive functions in amateur boxers compared to controls.


Involvement of two distinct killing mechanisms in bystander target cell lysis induced by a cytotoxic T lymphocyte clone.
Cytotoxic T lymphocyte (CTL) can lyse target cells by mainly two different mechanisms including granule exocytosis- and Fas-based cytotoxicity. In addition, CTL also lyse bystander target cells. In this study, we examined whether these two different killing mechanisms also cause bystander target cell lysis. EL-4 cells, representing bystander target cells, were incubated with CD8+ CTL clone B7B7 and antigen-treated P815 cells. EGTA-MgCl2 inhibited bystander lysis and reduced the release of BLT esterase. In addition, lysis of Fas-negative bystander cells (thymocytes from C57BL/6J-lpr/lpr not expressing Fas antigen) was also detected. CTL preactivated with antigen-treated P815 cells maintained a killing activity on bystander cells in the presence of cycloheximide (CHX). Furthermore, the presence of anti-Fas mAb inhibited the lysis of EL-4 cells by CTL stimulated with anti-TCR mAb. Thus, our results suggest that granule exocytosis- and Fas-mediated signal pathways cause the lysis of bystander target cells.


Exercise effects on bone mineral density, falls, coronary risk factors, and health care costs in older women: the randomized controlled senior fitness and prevention (SEFIP) study.
Physical exercise affects many risk factors and diseases and therefore can play a vital role in general disease prevention and treatment of elderly individuals and may reduce costs. We sought to determine whether a single exercise program affects fracture risk (bone mineral density [BMD] and falls), coronary heart disease (CHD) risk factors, and health care costs in community-dwelling elderly women. We conducted a randomized, single-blinded, controlled trial from May 1, 2005, through July 31, 2008, recruiting women 65 years or older who were living independently in the area of Erlangen-Nuremberg, Germany. In all, 246 women were randomly assigned to an 18-month exercise program (exercise group) or a wellness program (control group). The exercise group (n = 123) performed a multipurpose exercise program with special emphasis on exercise intensity; the controls (n = 123) focused on well-being with a low-intensity, low-frequency program. The main outcome measures were BMD, the number of falls, the Framingham-based 10-year CHD risk, and direct health care costs. For the 227 women who completed the 18-month study, significant exercise effects were observed for BMD of the lumbar spine (mean [95% confidence interval (CI)] percentage of change in BMD [baseline to follow-up] for the exercise group: 1.77% [1.26% to 2.28%] vs controls: 0.33% [-0.24% to 0.91%]; P < .001), femoral neck (exercise group: 1.01% [0.37% to 1.65%] vs controls: -1.05% [-1.70% to -0.40%]; P < .001), and fall rate per person during 18 months (exercise group: 1.00 [0.76 to 1.24] vs controls: 1.66 [1.33 to 1.99]; P = .002). The 10-year CHD risk was significantly affected in both subgroups (absolute change for the exercise group: -1.96% [95% CI, -2.69% to -1.23%] vs controls: -1.15% [-1.69% to -0.62%]; P = .22), with no significant difference between the groups. The direct health care costs per participant during the 18-month intervention showed nonsignificant differences between the groups (exercise group: 2255 euros[95% CI, 1791 euros-2718 euros] vs controls: 2780 euros [2187 euros-3372 euros]; P = .20). Compared with a general wellness program, our 18-month exercise program significantly improved BMD and fall risk, but not predicted CHD risk, in elderly women. This benefit occurred at no increase in direct costs. clinicaltrials.gov Identifier: NCT00267839.


Asparagine synthesis in pea leaves, and the occurrence of an asparagine synthetase inhibitor.
Asparagine is present in the mature leaves of young pea (Pisum sativum cv Little Marvel) seedlings, and is synthesized in detached shoots. This accumulation and synthesis is greatly enhanced by darkening. In detached control shoots, [(14)C]aspartate was metabolized predominantly to organic acids and, as other workers have shown, there was little labeling of asparagine (after 5 hours, 3.1% of metabolized label). Addition of the aminotransferase inhibitor aminooxyacetate decreased the flow of aspartate carbon to organic acids and enhanced (about 3-fold) the labeling of asparagine. The same treatment applied to darkened shoots resulted in a substantial conversion of [(14)C]aspartate to asparagine, over 10-fold greater than in control shoots (66% of metabolized label), suggesting that aspartate is the normal precursor of asparagine.Only traces of glutamine-dependent asparagine synthetase activity could be detected in pea leaf or root extracts; activity was not enhanced by sulfhydryl reagents, oxidizing conditions, or protease inhibitors. Asparagine synthetase is readily extracted from lupin cotyledons, but yield was greatly reduced by extraction in the presence of pea leaf tissue; pea leaf homogenates contained an inhibitor which produced over 95% inhibition of an asparagine synthetase preparation from lupin cotyledons. The inhibitor was heat stable, with a low molecular weight. Presence of an inhibitor may prevent detection of asparagine synthetase in pea extracts and in Asparagus, where a cyanide-dependent pathway has been proposed to account for asparagine synthesis: an inhibitor with similar properties was present in Asparagus shoot tissue.


The influence of maltreatment history and out-of-home-care on children's language and social skills.
This study examined the extent to which maltreatment history and the characteristics of out-of-home care correlated with the language and social skills of maltreated children. Participants in this study were 82 maltreated children aged between 5 and 12 years of age. All children were residing with state-designated carers in out-of-home-care. The children were presented with standardised tests assessing language and social skills. Results showed that the sample performed significantly below the normative mean on both tests. Correlation analyses showed social skills, but not language skills were correlated with aspects of maltreatment history. The education level of the state-designated carer/s was correlated with the children's language skills; higher education level was associated with higher language skills. The study provides evidence that at the group level, language and social skills are poor in maltreated children. However, gains in language skills might be made via the out-of-home-care environment. Improvements in the social skills of maltreated children may require additional support.


Idiopathic generalised epilepsy of late onset: a separate nosological entity?
Seizure onset in idiopathic generalised epilepsies (IGE) is considered to be rare after the second decade of life. The authors aimed to explore age of seizure onset in patients with IGE and compare 'classical' onset to late onset cases. Patients with IGE, treated at the outpatient epilepsy clinic (Medical University of Innsbruck, Austria, 1985-2006, n=798) were retrospectively screened. The inclusion criteria were: diagnosis of IGE, more than two follow-up (FU) visits, duration of FU more than 1 year and normal brain imaging. The authors analysed demographic data, age of seizure onset, seizure types, syndromes, neuroimaging and EEG findings, seizure triggers and seizure freedom for 1 and 5 years at last FU. A total of 492 patients (mean age at seizure onset 14.6 years, range 0.1-55, SD 7.9) with IGE were identified: childhood absence epilepsy (n=113, range 1-55, SD 6.5), juvenile absence epilepsy (n=75, range 4-39, SD 5.1), juvenile myoclonic epilepsy (n=112, range 2-39, SD 5.7), and epilepsy with grand mal seizures on awakening (n=192 range 1-52, SD 17.3). Population was stratified into three groups: 28 patients with seizure onset at >30 years, 180 patients between 15 and 30 years and 284 patients <15 years. The distribution of seizure types and epilepsy syndromes differed significantly in a group comparison (p<0.001); seizure outcome and other clinical variables did not differ throughout the groups. Apart from age-related onset of seizure types and syndromes with a loose upper limit of onset age, patients with a late onset did not differ from their younger counterparts. These data do not support the view of IGE of late onset as a separate syndrome.


Extended Duration Treatment of Tobacco Dependence: A Systematic Review and Meta-Analysis.
Rationale: The American Thoracic Society (ATS) developed a clinical practice guideline on initiating pharmacologic treatment in tobacco-dependent adults. Controller pharmacotherapies treat tobacco dependence effectively when taken as prescribed, but relapse after pharmacologic discontinuation is common. Objectives: To evaluate the effectiveness and safety of initiating controller for an extended (>12 wk) versus a standard duration (6-12 wk) in tobacco-dependent adults. Methods: We systematically searched PubMed, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to December 2021 to identify randomized controlled trials comparing extended versus standard duration of controllers for tobacco-dependent adults. We conducted meta-analyses using the Mantel-Haenszel method with random effects model. Outcomes of interest include point-prevalent abstinence at 1-year follow-up or longer, relapse, adverse events, quality of life, and withdrawal symptoms. Subgroup analyses were conducted according to types of treatment and duration of extended therapy when feasible. We assessed the certainty of the estimate following the grading of recommendations, assessment, development and evaluation methodology. Results: We included 13 randomized controlled trials including 8,695 participants that directly compared extended- (>12 wk) versus standard-duration controller therapy with varenicline, bupropion, or nicotine replacement therapy. Compared with standard-duration controller therapy, extended-duration controller therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence (relative risk, 1.18; 95% confidence interval [CI], 1.05-1.33; moderate certainty). Extended-duration controller therapy probably reduced relapse compared with standard-duration controller therapy, assessed at 12-18 months after initiation of therapy (hazard ratio, 0.43; 95% CI, 0.29-0.64; moderate certainty). Moderate certainty evidence also suggested that extended-duration controller therapy probably did not increase risk of serious adverse events (relative risk, 1.37; 95% CI, 0.79-2.36). Conclusions: This systematic review supported the recommendation for extended-duration therapy with controllers. Further studies on optimal extended duration are warranted.


Reach trajectories reveal delayed processing of low spatial frequency faces in developmental prosopagnosia.
Developmental prosopagnosia (DP) is characterized by a selective deficit in face recognition despite normal cognitive and neurological functioning. Previous research has established configural processing deficits in DP subjects. Low spatial frequency (LSF) information subserves configural face processing. Using hybrid stimuli, here we examined the evolution of perceptual dynamics and integration of LSF information by DP subjects while they pointed to high spatial frequency (HSF) face targets. Permutation analysis revealed a 230-ms delay in LSF processing by DP subjects as compared to controls. This delayed processing is likely to contribute to the difficulties associated with face recognition in DP subjects and is reflective of their alleged reliance on local rather than global features in face perception. These results suggest that quick and efficient processing of LSF information is critical for the development of normal face perception.


Bridgehead nitrogen heterocycles which contain the quinazoline moiety -- synthesis and cycloaddition of 1,2-dihydroquinazoline 3-oxides.
A novel synthesis of 1,2-disubstituted 1,2-dihydroquinazoline 3-oxides 8 and the first ever examples of 1,3-dipolar trapping of these nitrones to homonuclear dipolarophiles is described. The new dipoles 8 reacted with N-methyl maleimide, generating diastereomeric adducts 14-16. In the reaction between 8 and dimethyl acetylenedicarboxylate, primary cycloadducts 17 and/or stable rearrangement products, azomethine ylides 18, are formed depending on the substitution pattern of the dipole. The structure of 18c is unambiguously assigned by X-ray crystallographic analysis. An X-ray crystal structure determination is also presented for the cyclopropylisoxazoloquinazoline 22 formed by a [3 + 2] addition of 8a to 21, the dimethyl acetylenedicarboxylate tetramer.


Prevalence of asymptomatic poliovirus infection in older children and adults in northern India: analysis of contact and enhanced community surveillance, 2009.
In 2009, enhanced poliovirus surveillance was established in polio-endemic areas of Uttar Pradesh and Bihar, India, to assess poliovirus infection in older individuals. In Uttar Pradesh, stool specimens from asymptomatic household and neighborhood contacts of patients with laboratory-confirmed polio were tested for polioviruses. In Bihar, in community-based surveillance, children and adults from 250 randomly selected households in the Kosi River area provided stool and pharyngeal swab samples that were tested for polioviruses. A descriptive analysis of surveillance data was performed. In Uttar Pradesh, 89 of 1842 healthy contacts of case patients with polio (4.8%) were shedding wild poliovirus (WPV); 54 of 85 (63.5%) were ≥5 years of age. Shedding was significantly higher in index households than in neighborhood households (P<.05). In Bihar, 11 of 451 healthy persons (2.4%) were shedding WPV in their stool; 6 of 11 (54.5%) were ≥5 years of age. Mean viral titer was similar in older and younger children. A high proportion of persons≥5 years of age were asymptomatically shedding polioviruses. These findings provide indirect evidence that older individuals could have contributed to community transmission of WPV in India. Polio vaccination campaigns generally target children<5 years of age. Expanding this target age group in polio-endemic areas could accelerate polio eradication.


Sexually dimorphic expression of androgen receptor immunoreactivity by somatostatin neurones in rat hypothalamic periventricular nucleus and bed nucleus of the stria terminalis.
Gonadal steroids exert important regulatory actions on the hypothalamic neurones regulating growth hormone secretion and are believed to play a role in generating its sexually dimorphic pattern of secretion. Recent evidence indicates that estrogen actions on one of these neural populations, the periventricular somatostatin (SOM) neurones, are likely to be indirect as they do not possess nuclear estrogen receptors in either sex although androgen receptors (ARs) have been reported within these cells in male rats. The present study has used double-labelling immunocytochemistry procedures to examine whether sex differences exist in AR expression by SOM neurones located in the periventricular nucleus and bed nucleus of the stria terminalis (BNST). Within the hypothalamus, SOM-immunoreactive neurones were found concentrated in the periventricular nucleus while both anterior and posterior divisions of the BNST contained scattered populations of SOM cells. Cells immunoreactive for the AR were detected in all of these areas. Although the intensity of AR cell nuclei staining was equivalent in males and females in regions such as the lateral septum, the intensity of AR staining in many individual cells of the periventricular nucleus and posterior BNST of the female was reduced when compared with the male. Double-labelling experiments revealed that approximately 40% of periventricular SOM neurones expressed AR immunoreactivity in the male compared with significantly (P < 0.01) fewer cells in the female (approximately 7%). In the BNST, double-labelled cells were only detected within the principle encapsulated, interfascicular and transverse nuclei of its posterior division. Approximately 60% of SOM cells in these nuclei expressed AR immunoreactivity in the male while significantly (P < 0.01) fewer did so in the female (approximately 25%). These results indicate that substantial sex differences exist in AR expression by SOM neurones in both the periventricular nucleus and BNST. Such differences in AR expression by periventricular SOM cells may contribute to their sexuality dimorphic nature and, consequently, sex differences in growth hormone secretion.


Metabolic syndrome as a predictor of endometrial polyps in postmenopausal women.
The aim of the study was to evaluate clinical predictive factors for endometrial polyps in postmenopausal women compared with postmenopausal women without polyps. In this cross-sectional study, 132 Brazilian women with a histopathological diagnosis of endometrial polyps were compared with 264 women without endometrial alterations (control). The study group included women aged at least 45 years with amenorrhea for at least 12 months, who underwent hysteroscopic polypectomy. The control group consisted of women aged at least 45 years with amenorrhea for at least 12 months, without postmenopausal bleeding and endometrial thickness less than 5 mm by transvaginal ultrasonography. Clinical, anthropometric (body mass index and waist circumference), laboratory, and ultrasonographic data were collected to evaluate predictive factors for endometrial polyps. The Student's t test, χ test, and logistic regression (odds ratio [OR]) were used for statistical analysis. A higher percentage of women with polyps were obese (72%) when compared with control (39%) (P < 0.0001). Waist circumference was greater among women with polyps (P = 0.0001). The incidence of diabetes, hypertension, and dyslipidemia was higher among women with endometrial polyps (P < 0.0001). According to the diagnostic criteria of the US National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III), 48.5% of the women with polyps and 33.3% of the controls were classified as having metabolic syndrome (MetS) (P = 0.004). The risk of endometrial polyps was higher in women with body mass index at least 25 kg/m (OR = 4.66; 95% CI 2.16-10.05); glucose at least 100 mg/dL (OR = 2.83; 95% CI 1.36-5.90); dyslipidemia (OR = 7.02; 95% CI 3.70-13.32); diabetes (OR = 2.58; 95% CI 1.05-6.32); and MetS (OR = 2.76; 95% CI 1.18-6.46) when compared with control, adjusted for age, and time since menopause. In postmenopausal women, obesity, dyslipidemia, hyperglycemia, and the presence of MetS were predictive factors for endometrial polyps.


Quantitative monitoring of serum hepatitis B virus DNA and blood lymphocyte subsets during combined prednisolone and interferon-alpha therapy in patients with chronic hepatitis B.
Several investigators have reported a significantly reduced CD4/CD8 ratio, as defined by monoclonal antibodies, in the peripheral blood of Caucasian patients with chronic active hepatitis B (CAHB). In Asian patients with chronic hepatitis B, quantitative analyses of subpopulations of peripheral blood lymphocytes have not been able to confirm these findings. In this work, we analysed the frequency of peripheral blood lymphocyte subsets in 10 Chinese patients with histologically proven CAHB and seven healthy Chinese individuals. Four of the 10 CAHB patients received combined prednisolone/interferon-alpha2b (IFN-alpha2b) therapy. Peripheral blood samples were consecutively collected for analysis of lymphocyte subpopulations using an indirect immunofluorescence (IF) method, and hepatitis B virus (HBV) DNA was quantified by a chemiluminescent, molecular-hybridization assay. Peripheral blood mononuclear cells from seven Chinese control individuals comprised 63 +/- 3% CD3+ cells, of which 41 +/- 4% were of CD4+ and 23 +/- 2% of CD8+ subsets. The mean CD4/CD8 ratio in the healthy controls was 1.9 (95% confidence interval = 1.1-2.7). The CD4/CD8 ratios were significantly reduced (P < 0.01) in the 10 patients with chronic hepatitis B, compared with those of the controls, owing to a significant increase in the number of CD8+ cells (P < 0.005). During the treatment with prednisolone, a significant increase in the CD4/CD8 ratio was observed in all treated patients. This increase was mainly caused by a decrease in the number of CD8+ cells and was accompanied by an increase in serum HBV DNA levels, which peaked during the latter part of the prednisolone cycle. During the treatment with IFN-alpha2b, a second increase in the CD4/CD8 ratio was observed, which was caused by an increase in CD4+ cells. A marked decrease in viral load was observed, during treatment with IFN-alpha2b, in patients with HBV DNA levels below 10 000 pg ml-1. Our data indicate that the CD4/CD8 ratios in Chinese CAHB patients do not differ from those of Caucasian patients with CAHB, when analysed using similar methods for the enumeration of lymphocyte subsets. Profound effects on cellular distribution and viral replication were noted during the combined prednisolone/IFN-alpha2b therapy. Additional studies of the modulatory effect of the combined therapy on the distribution of lymphocyte subsets and cytokine profiles in relation to the therapeutic outcome of HBV infection are warranted.


Three-Dimensional Structure and Optimization of the Metallo-β-Lactamase Inhibitor Aspergillomarasmine A.
The aminopolycarboxylic acid aspergillomarasmine A (AMA) is a natural Zn2+ metallophore and inhibitor of metallo-β-lactamases (MBLs) which reverses β-lactam resistance. The first crystal structure of an AMA coordination complex is reported and reveals a pentadentate ligand with distorted octahedral geometry. We report the solid-phase synthesis of 23 novel analogs of AMA involving structural diversification of each subunit (l-Asp, l-APA1, and l-APA2). Inhibitory activity was evaluated in vitro using five strains of Escherichia coli producing globally prevalent MBLs. Further in vitro assessment was performed with purified recombinant enzymes and intracellular accumulation studies. Highly constrained structure-activity relationships were demonstrated, but three analogs revealed favorable characteristics where either Zn2+ affinity or the binding mode to MBLs were improved. This study identifies compounds that can further be developed to produce more potent and broader-spectrum MBL inhibitors with improved pharmacodynamic/pharmacokinetic properties.


"We saw that jealousy can also bring violence": A qualitative exploration of the intersections between jealousy, infidelity and intimate partner violence in Rwanda and Uganda.
Efforts to prevent intimate partner violence (IPV) have been informed by emerging research on common triggers of IPV and the importance of engaging with couple dynamics. This paper reports on secondary data analysis from the qualitative evaluations of the SASA! intervention in Uganda, (conducted in 2012 involving 40 community members) and the Indashyikirwa intervention in Rwanda, (conducted between 2014 and 2018 involving 14 couples and 36 other stakeholders). It explores the under-researched linkages between romantic jealousy and IPV, and describes how these interventions mitigated it. A qualitative approach using interviews and focus groups with women and men was used. Overall, jealousy was common in both settings, and led to relationship challenges including breakdown of trust; quarrels about resources; conflict, controlling behaviours, and ultimately, physical and emotional IPV. Jealousy was seen to operate through different gendered pathways. Participants described women to question men about their whereabouts and intentions because of jealousy or the suspicion of infidelity, whereas participants described men to be jealous or suspicious of women socialising with, or attracting the attention of, other men and using violence in response. Through gender transformative strategies, SASA! and Indashyikirwa were described by participants to reduce the contribution of romantic jealousy to conflict and violence by encouraging improved relationship faithfulness and honesty; supporting reduced suspicion through improved relationship trust and communication; and identifying jealousy and suspicion of, or real infidelity, as direct triggers of IPV. While these programmes show promising results, gaps remain including a lack of standardised measures of the multidimensional concept of romantic jealousy. Recognition that programmes should be evaluated for their ability to reduce romantic jealousy when identified as a trigger for IPV in a specific context should also be emphasised. More research is also needed on the forms, gendered pathways, and consequences of romantic jealousy to inform context-specific programming.


Diagnosis, evaluation and treatment of carcinoma in situ of the urinary bladder: the state of the art.
Urothelial carcinoma in situ (CIS) is regarded as a precursor of invasive bladder carcinoma. Although relatively uncommon as a primary entity, CIS is frequently seen in conjunction with other bladder tumors and represents a significant source of difficulty for surveillance of patients with known bladder cancer. CIS lesions are difficult to detect by cystoscopic examination or by currently available screening markers. Urothelial CIS is infrequently reported in the literature as a primary process; however, a wide variety of emerging methodologies are becoming available for screening and follow-up of bladder cancer. Most new methods demonstrate sensitivity and specificity similar to the current standard of urine cytology and cystoscopy. Detection of high-grade lesions such as CIS by these methods appears generally better than detection of low-grade lesions. Current molecular evidence suggests that a spectrum of genetic aberrations including p53 mutations are strongly associated with the potentially invasive CIS phenotype in contrast to low-grade papillary and hyperplastic lesions. These low-grade lesions frequently recur but infrequently become invasive. Patients with high-grade lesions including CIS and high-grade papillary tumors warrant aggressive treatment and life-long surveillance.