Rotator cuff disease.
The important role played by the rotator cuff in the stability and movement of the glenohumeral joint make it susceptible to damage and injury in patients of all age groups. A number of extrinsic and intrinsic mechanisms have been described for the development of rotator cuff disease, although it is more likely that the actual etiology in any one individual is multifactorial. The key to successful management in a particular patient is an accurate diagnosis of the underlying cause by thorough clinical examination and the use of appropriate investigations. The mainstay of treatment of patients with rotator cuff disease is nonoperative. Surgical intervention is usually considered only after failure of at least 6 months of conservative therapy. However, there are a few situations where early surgical intervention is indicated.


Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.


Does breaking up prolonged sitting improve cognitive functions in sedentary adults? A mapping review and hypothesis formulation on the potential physiological mechanisms.
Prolonged (excessive) sitting is detrimentally associated with cardiovascular, metabolic and mental health. Moreover, prolonged sitting has been associated with poor executive function, memory, attention and visuospatial skills, which are important cognitive aspects of work performance. Breaking up prolonged sitting with standing or light-intensity exercises at the workplace is recognized as a potential measure in improving cognition. However, preliminary evidence, primarily from acute laboratory experiments, has enabled formulating hypothesis on the possible mechanistic pathways. Hence, the aim of this mapping review is to gather preliminary evidence and substantiate possible physiological mechanisms underpinning the putative effects of breaking prolonged sitting on improving cognitive function among sedentary office workers. We searched four databases to identify relevant studies that explored the effects of uninterrupted sitting on cognitive function. First, we introduce how prolonged sitting increases the risks of hyperglycemia, autonomic stability, inflammation, adverse hormonal changes and restrictions in cerebral blood flow (CBF) and alters cognitive function. Second, we elucidate the direct and indirect effects of breaking up prolonged sitting time that may prevent a decline in cognitive performance by influencing glycaemic variability, autonomic stability, hormones (brain derived neurotrophic factor, dopamine, serotonin), vascular functions, and CBF. We highlight the importance of breaking up prolonged sitting on metabolic, vascular and endocrine functions, which in turn may improve cognitive functions and eventually foster work productivity. Improved synaptic transmission or neuroplasticity due to increased brain glucose and mitochondrial metabolism, increased endothelial shear and CBF, increased brain neurotrophic factors (dopamine) and accelerated anti-inflammatory functions are some of the hypothetical mechanisms underpinning improved cognitive functions. We postulate that improving cognitive function by breaking up prolonged sitting periods is biologically plausible with the myriad of (suggested) physiological mechanisms. Future experimental studies to ascertain the aforementioned hypothetical mechanisms and clinical trials to break sedentary behavior and improve cognitive functions in sedentary office workers are warranted.


Pituitary adenomas producing growth hormone in acromegalic patients.
Growth hormone was shown in histological sections of 25 pituitary adenomas from acromegalic patients by means of the unlabelled peroxidase-antiperoxidase (PAP) technique. On the basis of the numbers of cytoplasmic granules, the cells of the adenomas were of two types: densely granulated and sparsely granulated. The densely granulated cells had abundant cytoplasm containing numerous granules, whereas the sparsely granulated cells had little cytoplasm with scanty granules. Depending on the predominant cell type the adenomas were also classified as densely granulated or sparsely granulated: 21 of the 25 adenomas (84%) were densely granulated and four (16%) sparsely granulated. There was some variation, however, in the relative numbers of the two types of cell from one part of an adenoma to another, a feature consistent with one type of cell in different phases of activity. There was no significant difference in mean serum growth hormone concentrations between the two groups, and granularity of the adenomas in histological sections did not therefore correlate with secretory activity. Nine adenomas showed extrasellar extension. The mean serum growth hormone concentration in these cases was lower than the mean of the adenomas confined to the sella turcica. Thus the size of the tumour did not correlate with the serum growth hormone concentration. Three of the four adenomas in the sparsely granulated group showed extrasellar extension, compared with 6 of 21 classified as densely granulated. This suggests that sparsely granulated adenomas have a more aggressive pattern of behaviour, but histological evidence for this was lacking.


Membrane-type 1 metalloproteinase is upregulated in microglia/brain macrophages in neurodegenerative and neuroinflammatory diseases.
We previously reported that glioma cells induce the expression of membrane-type 1 metalloproteinase (MT1-MMP or MMP-14) in tumor-associated microglia/macrophages and promote tumor growth, whereas MMP-14 expression in microglia under physiological conditions is very low. Here, we show that the increase in MMP-14 expression is also found in microglia/macrophages associated with neurodegenerative and neuroinflammatory pathologies in mouse models as well as in human biopsies or post-mortem tissue. We found that microglial/macrophage MMP-14 expression was upregulated in Alzheimer's disease tissue, in active lesions of multiple sclerosis, and in tissue from stage II stroke as well as in the corresponding mouse models for the human diseases. In contrast, we observed no upregulation for MMP-14 in microglia/macrophages in the early phase of stroke or in the corresponding mouse model, in human amyotrophic lateral sclerosis (ALS) tissue or in a mouse model of ALS as well as in human cases of acute brain trauma. These data indicate that MMP-14 expression is not a general marker for activated microglia/macrophages but is upregulated in defined stages of neuroinflammatory and neurodegenerative diseases and that there is generally a good match between mouse models and human brain pathologies.


Brief Online Self-help Exercises for Postnatal Women to Improve Mood: A Pilot Study.
Giving birth and adjusting to a new baby can be difficult and stressful for new mothers. Negative mood may occur during this time and can affect women, their parenting and the infant's development. This pilot study evaluated a brief online self-help intervention designed to promote positive mood in mothers of babies and toddlers. Women in the UK who had given birth within the previous 18 months were randomly allocated to the online self-help intervention (n = 40) or active comparison group exercise (n = 40) which was matched for time and structure. Mood was measured before and after the intervention. Acceptability was examined at the end of the trial. The self-help intervention was acceptable to the majority of women and significantly increased positive mood compared to the comparison condition. This effect persisted after controlling for self-esteem, anxiety and depression. These results suggest that a simple self-help intervention focused on changing beliefs about oneself as a mother can have an immediate impact on women's mood. Further research is need to see whether these improvements continue long-term and what processes underlie these improvements.


Implementation of transmural disease management in patients admitted with advanced heart failure.
The objective of this study was to assess the feasibility and impact on readmissions of transmural disease management across the borders of the cardiology department in patients with advanced heart failure (HF). Consecutive patients, readmitted within one year for advanced HF by a dedicated specialist (n = 55), were followed for 22 +/- 10 months after implementation of a hospitalwide transmural disease management strategy. Participants received a tag in their electronic medical record, triggering a HF caregiver contact, with subsequent guideline-recommended, protocol-driven care on each cardiac or non-cardiac hospitalization as well as outpatient evaluation. Upon transition to outpatient follow-up, patients were instructed to call the HF caregiver with any question at low threshold. Readmission rates were prospectively collected. Despite receiving adequate treatment with neurohumoral blockers, patients (71 +/- 11 years; ejection fraction 35 +/- 13%) had spent 4% (27%) of the year preceding study inclusion in hospital, with 73% admitted once, 20% twice, and 7% more than twice for acute decompensated HF (ADHF). During the study, patients were exposed to 6 +/- 4 dedicated HF caregiver contacts. Participation in remote device monitoring increased from 31% to 92%, with 1 (0-3) additional phone contacts per patient-year of follow-up in this subgroup (n = 24). All-cause mortality and readmission rates for ADHF were 10% and 25% after one year, and 19% and 39% after 2 years, respectively. Follow-up time spent in hospital decreased significantly to 2% (16%) (P value = 0.047). Follow-up of advanced HF patients through transmural disease management is feasible and associated with favourable clinical outcome.


The role of the COVID-19 pandemic as a risk factor for suicide: What is its impact on the public mental health state today?
The phenomenon of suicide is a much studied but still little-known issue. In this particular period of health emergency, quarantine and mandatory restrictions could play a role in the genesis of fatal events or suicide attempts not only in people at risk. However, this issue has not yet been adequately addressed in the literature. The influence of the global pandemic could change the way suicide cases are analyzed; in the future, it is necessary to reconsider and analyze the various risk groups by population but above all to evaluate new methods of intervention for avoiding the increase in fatal events related to the current emergency whose duration is still unknown. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


A naturalistic prospective open study of the effects of adjunctive therapy of sexual dysfunction in chronic PTSD patients.
Post-traumatic Stress Disorder (PTSD) symptoms cause dysfunction in broad areas of patients' lives and those of their families. Sexual dysfunction (SD) is common in these patients and aggravates their distress, affecting overall sexual activity, desire, arousal, orgasm, activity and satisfaction. PTSD clinic patients are frequently referred for consultation and treatment in the SD clinic. This prospective naturalistic follow-up study of a random group of patients was intended to evaluate response to pharmacologic and psychotherapeutic interventions for SD, in terms of both sexual functioning and overall symptomatology. Ten patients fulfilling DSM-IV diagnostic criteria for PTSD (one woman and nine men) were recruited. Treatment for the sexual symptoms was tailored individually and was administered in addition to the continuing (stable) treatment in the PTSD clinic. After two months of treatment for the sexual symptoms, statistically significant improvements in all domains of sexual functioning were observed. In parallel, statistically significant improvements in all domains of the Impact of Events Scale scores were observed, both on the avoidance and intrusive subscales. There were no significant differences in response to treatment in terms of time elapsed since the onset of PTSD, or the pattern or severity of sexual and PTSD symptoms. The results of this modest study demonstrate the importance of relating to the SD of PTSD patients irrespective of the duration or severity of their disorder. In this mixed group of PTSD patients with varied duration of symptoms, both SD and PTSD core symptoms improved significantly in response to individually tailored adjunctive treatment of the SD.


Exploiting sample variability to enhance multivariate analysis of microarray data.
Biological and technical variability is intrinsic in any microarray experiment. While most approaches aim to account for this variability, they do not actively exploit it. Here, we consider a novel approach that uses the variability between arrays to provide an extra source of information that can enhance gene expression analyses. We develop a method that uses sample similarity to incorporate sample variability into the analysis of gene expression profiles. This allows each pairwise correlation calculation to borrow information from all the data in the experiment. Results on synthetic and human cancer microarray datasets show that the inclusion of this information leads to a significant increase in the ability to identify previously characterized relationships and a reduction in false discovery rate, when compared to a standard analysis using Pearson correlation. The information carried by the variability between arrays can be exploited to significantly improve the analysis of gene expression data. Matlab script files are available from the author. Supplementary data are available at Bioinformatics online.


Mediterranean diet and preserved brain structural connectivity in older subjects.
The Mediterranean diet (MeDi) has been related to a lower risk of Alzheimer's disease; yet, the underlying mechanisms are unknown. We hypothesized that protection against neurodegeneration would translate into higher gray matter volumes, whereas a specific association with preserved white matter microstructure would suggest alternative mechanisms (e.g., vascular pathways). We included 146 participants from the Bordeaux Three-City study nondemented when they completed a dietary questionnaire and who underwent a 3-T magnetic resonance imaging at an average of 9 years later, including diffusion tensor imaging. In multivariate voxel-by-voxel analyses, adherence to the MeDi was significantly associated with preserved white matter microstructure in extensive areas, a gain in structural connectivity that was related to strong cognitive benefits. In contrast, we found no relation with gray matter volumes. The MeDi appears to benefit brain health through preservation of structural connectivity. Potential mediation by a favorable impact on brain vasculature deserves further research.


Cerebral magnetic resonance image segmentation using data fusion.
A semiautomated method is described for segmenting dual echo MR head scans into gray and white matter and CSF. The method is applied to brain scans of 80 healthy children and adolescents. A probabilistic data fusion equation was used to combine simultaneously acquired T2-weighted and proton density head scans for tissue segmentation. The fusion equation optimizes the probability of a voxel being a particular tissue type, given the corresponding probabilities from both images. The algorithm accounts for the intensity inhomogeneities present in the images by fusion of local regions of the images. The method was validated using a phantom (agarose gel with iron oxide particles) and hand-segmented images. Gray and white matter volumes for subjects aged 20-30 years were close to those previously published. White matter and CSF volume increased and gray matter volume decreased significantly across ages 4-18 years. White matter, gray matter, and CSF volumes were larger for males than for females. Males and females showed similar change of gray and white matter volumes with age. This simple, reliable, and valid method can be employed in clinical research for quantification of gray and white matter and CSF volumes in MR head scans. Increase in white matter volume may reflect ongoing axonal growth and myelination, and gray matter reductions may reflect synaptic pruning or cell death in the age span of 4-18 years.


Fluorochrome-based definition of naturally occurring Foxp3(+) regulatory T cells of intra- and extrathymic origin.
Under physiological conditions, studies on the biology of naturally induced Foxp3(+) Treg cells of intra- and extrathymic origin have been hampered by the lack of unambiguous markers to discriminate the mature progeny of such developmental Treg-cell sublineages. Here, we report on experiments in double-transgenic mice, in which red fluorescent protein (RFP) is expressed in all Foxp3(+) Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3(+) Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP(+) GFP(+) ) and extrathymic (RFP(+) GFP(-) ) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3(+) Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3(+) Treg cells represent distinct phenotypic and functional sublineages.


Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis.
Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis. One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL. Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores. Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.


Drivers of household food availability in sub-Saharan Africa based on big data from small farms.
We calculated a simple indicator of food availability using data from 93 sites in 17 countries across contrasted agroecologies in sub-Saharan Africa (>13,000 farm households) and analyzed the drivers of variations in food availability. Crop production was the major source of energy, contributing 60% of food availability. The off-farm income contribution to food availability ranged from 12% for households without enough food available (18% of the total sample) to 27% for the 58% of households with sufficient food available. Using only three explanatory variables (household size, number of livestock, and land area), we were able to predict correctly the agricultural determined status of food availability for 72% of the households, but the relationships were strongly influenced by the degree of market access. Our analyses suggest that targeting poverty through improving market access and off-farm opportunities is a better strategy to increase food security than focusing on agricultural production and closing yield gaps. This calls for multisectoral policy harmonization, incentives, and diversification of employment sources rather than a singular focus on agricultural development. Recognizing and understanding diversity among smallholder farm households in sub-Saharan Africa is key for the design of policies that aim to improve food security.


[A transmaxillary transnasal approach to tumors of the base of the skull].
The microsurgical transmaxillary transnasal approach provides a wide access to the midline of the skull base. Since 1994 the approach was performed in 11 patients while resecting malignant and benign skull base tumors by involving the cribriform plate, orbit, maxillary and sphenoidal sinuses, nasal cavity, clivus, and cavernous sinus. The technique is suitable for extradural tumors of the skull base and can be combined with transcranial approaches for more extensive lesions.


Urinary free cortisol in the diagnosis of Cushing's syndrome: how useful?
Cushing's syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. To confirm the clinical suspicion, biochemical tests are needed. These biochemical tests include the measurement of excess total endogenous cortisol secretion assessed by 24-hour urinary free cortisol (UFC), loss of the normal feedback of the hypothalamo-pituitary-adrenal axis assessed by suppressibility after dexamethasone testing, and disturbance of the normal circadian rhythm of cortisol secretion assessed by midnight serum or salivary cortisol. We searched the Medline, Pubmed, journal articles, WHO publications and reputable textbooks relating to Cushing's syndrome using publications from 1995 to 2011. UFC has been the classic screening test used to confirm hypercortisolemia as the first step in diagnostic work-up of Cushing's syndrome. Its long-term use in clinical practice has led to emergence of significant evidence regarding the utility of UFC in the diagnosis of Cushing's syndrome. UFC would have been a simple diagnostic tool to use but for the drawbacks in the sample collection, different laboratory methods of assay, not easily determined normal range. UFC use as a screening test is not strongly favoured because cortisol is not uniformly secreted during the day, and the increased prevalence of mild, preclinical or cyclic Cushing's syndrome. A very high level of UFC negates the need for other test procedures in patients with obvious symptoms and signs of Cushing's syndrome. We therefore suggest that UFC should be used with other screening tests for Cushing's syndrome to increase diagnostic yield.


Overcoming IMiD resistance in T-cell lymphomas through potent degradation of ZFP91 and IKZF1.
Immunomodulatory (IMiD) agents like lenalidomide and pomalidomide induce the recruitment of IKZF1 and other targets to the CRL4CRBN E3 ubiquitin ligase, resulting in their ubiquitination and degradation. These agents are highly active in B-cell lymphomas and a subset of myeloid diseases but have compromised effects in T-cell lymphomas (TCLs). Here, we show that 2 factors determine resistance to IMiDs among TCLs. First, limited CRBN expression reduces IMiD activity in TCLs but can be overcome by newer-generation degrader CC-92480. Using mass spectrometry, we show that CC-92480 selectively degrades IKZF1 and ZFP91 in TCL cells with greater potency than pomalidomide. As a result, CC-92480 is highly active against multiple TCL subtypes and showed greater efficacy than pomalidomide across 4 in vivo TCL models. Second, we demonstrate that ZFP91 functions as a bona fide transcription factor that coregulates cell survival with IKZF1 in IMiD-resistant TCLs. By activating keynote genes from WNT, NF-kB, and MAP kinase signaling, ZFP91 directly promotes resistance to IKZF1 loss. Moreover, lenalidomide-sensitive TCLs can acquire stable resistance via ZFP91 rewiring, which involves casein kinase 2-mediated c-Jun inactivation. Overall, these findings identify a critical transcription factor network within TCLs and provide clinical proof of concept for the novel therapy using next-generation degraders.


Protein kinase C downregulation induces senescence via FoxO3a inhibition in HCT116 and HEK293 cells.
We investigated the impact of protein kinase C (PKC) on cellular senescence. The PKC activity and expression of conventional PKC (cPKC) and atypical PKC (aPKC) isoforms decreased during replicative senescence in IMR-90 cells. Forced inhibition of cPKC or aPKC induced the activation of senescence markers, including senescence-associated β-galactosidase activity and reactive oxygen species (ROS)-p53-p21Cip1/WAF1 axis in HCT116 and HEK293 cells. PKC inhibition triggered the nuclear exportation of FoxO3a via stimulation of AKT-mediated phosphorylation of FoxO3a, and thereby decreased the transcription of FoxO3a target genes. Conversely, ectopic expression of the PKC isoforms led to stimulation of the nuclear import of FoxO3a and expression of the FoxO3a target genes. Ectopic FoxO3a expression attenuated ROS accumulation and senescent phenotypes induced by PKC inhibition. Therefore, this study suggests for the first time that downregulation of PKC induces senescence through the AKT-FoxO3a-ROS-p53-p21Cip1/WAF1 pathway in HCT116 and HEK293 cells.


Dendritic cell-based vaccines: Shining the spotlight on signal 3.
Dendritic cell (DC)-based anticancer vaccines have yielded disappointing results in a multitude of clinical trials. New data suggest that the clinical efficacy of DC-based vaccines may be dependent on the paracrine production of interleukin-12 in the course of antigen presentation and the consequent development of therapeutic Type 1 CD8+ T-cell immunity.


Temperature changes produced by the injection of catecholamines and 5-hydroxytryptamine into the cerebral ventricles of the conscious mouse.
1. Changes in temperature were determined following injection of noradrenaline, adrenaline, isoprenaline, dopamine and 5-hydroxytryptamine (5-HT) into the cerebral ventricles of the conscious mouse.2. Noradrenaline (1-20 mug) and dopamine (10-160 mug) caused falls in body temperature. Adrenaline (1-20 mug) caused a slight and transient rise in body temperature followed by a fall. Isoprenaline (5-20 mug) caused a rise in body temperature, hypothermia only occurring after very high doses (200 mug) of this catecholamine.3. alpha- and beta-adrenergic blocking agents, phentolamine (> 2 mug) and propranolol (> 5 mug) respectively, caused falls in body temperature when injected into the cerebral ventricles of the mouse.4. Specific drug antagonism studies were limited owing to the intrinsic effects of the alpha- and beta-adrenergic blocking agents. However, some evidence was obtained to indicate that noradrenaline mediated its effects through a central alpha-type adrenergic receptor.5. 5-HT (10-160 mug) caused a fall in body temperature. The action of this indoleamine and the catecholamines in regard to thermoregulatory function is discussed.


Association of Perioperative Opioid Prescriptions With Risk of Complications After Tonsillectomy in Children.
Practice guidelines recommend nonopioid medications in children after tonsillectomy, but to date, studies have not used recent national data to assess perioperative opioid prescribing patterns or the factors associated with these patterns in this population. Closing this knowledge gap may help in assessing whether such prescribing and prescription duration could be safely reduced. To assess national perioperative opioid prescribing patterns, clinical and demographic factors associated with these patterns, and association between these patterns and complications in children after tonsillectomy compared with children not using opioids. This cohort analysis used the 2016 to 2017 claims data from the database of a large national private insurer in the United States. Opioid-naive children aged 1 to 18 years with a claims code for tonsillectomy with or without adenoidectomy between April 1, 2016, and December 15, 2017, were identified (n = 22 567) and screened against the exclusion criteria. The final sample included 15 793 children. The percentage of children with 1 or more perioperative fills (prescription drug claims for opioids between 7 days before to 1 day after tonsillectomy) was calculated, along with the duration of perioperative prescriptions (days supplied). Linear regression was used to identify the demographic and clinical factors associated with the duration of perioperative opioid prescriptions. Logistic regression was used to assess the association between having 1 or more perioperative fills and their duration and the risk of return visits 2 to 14 days after tonsillectomy for pain or dehydration, secondary hemorrhage, and constipation compared with children not using opioids. Among 15 793 children, the mean (SD) age was 7.8 (4.2) years, 12 807 (81.1%) were younger than 12 years, 2986 (18.9%) were between 12 and 18 years of age, and 8289 (52.6%) were female. In total, 9411 (59.6%) children had 1 or more perioperative fills, and the median (25th-75th percentile) duration was 8 (6-10) days; 6382 had no perioperative fills. The probability of having 1 or more perioperative fills and the duration of prescription varied across US census divisions. Having 1 or more perioperative fills was not associated with return visits for pain or dehydration (adjusted odds ratio [AOR], 1.13; 95% CI, 0.95-1.34) or secondary hemorrhage (AOR, 0.90; 95% CI, 0.73-1.10) compared with children not using opioids, but it was associated with increased risk of return visits for constipation (AOR, 2.02; 95% CI, 1.24-3.28). Duration was not associated with return visits for complications. These findings suggest that reducing perioperative opioid prescribing and the duration of perioperative opioid prescriptions may be possible without increasing the risk of these complications.


Geographical variations in the epidemiology of bacterial sexually transmitted infections in Manitoba, Canada.
Feasible epidemiological approaches are required to make a better assessment of the stage of an epidemic and to monitor its transition through various phases. Application of the Lorenz curve and Gini coefficient to summarise the inequality in STD incidence rates between jurisdictions in Manitoba, Canada, was found to provide useful insights into the concentration of these epidemics over time and thus their transition through epidemic phases. Further exploration of the statistical properties of these and other indices of inequality and their potential application to STD epidemiology is warranted. New epidemiological tools are also required for better monitoring of the impact of prevention and control activities and to inform the content of these activities.


Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for the evidence.
To investigate the evidence leading to nitrofurantoin contraindication in patients with a creatinine clearance (CrCl) below 60 mL/min. Literature was searched in PubMed (1965-June 2012) by using the key words and MeSH terms urinary tract infections-drug therapy, chronic kidney insufficiency, kidney diseases, pharmacokinetics, safety, and efficacy, combined with nitrofurantoin. Articles were limited to the English language. References from the identified studies, Food and Drug Administration-approved product information packets, drug information resources, and pharmacology books were also reviewed. The contraindication of nitrofurantoin in patients with a CrCl below 60 mL/min was included in the product information packets sometime between 1988 and 2003. The 1988 Macrodantin product information indicated a CrCl cutoff level of 40 mL/min, but the current contraindication of less than 60 mL/min is found in the 2003 Macrobid product information. It is unclear when and why this change occurred, but it may have followed the work of Sachs and colleagues in 1968, who reported very little drug recovery in the urine of patients with a CrCl below 60 mL/min. This and previous studies have several and severe limitations, such as the inclusion of a small number of patients, an undefined or poorly defined method to determine CrCl and renal impairment, measurement of amounts of nitrofurantoin excreted in the urine instead of urinary concentrations, and most importantly, a lack of clinical efficacy end points. More recently, a chart review on clinical cure of urinary tract infections treated with nitrofurantoin provided grounds for further investigations on the utility of this drug for patients with a CrCl of 60 mL/min or lower. Concerns of increased risks of serious adverse reactions in patients with reduced renal function have further limited the use of nitrofurantoin. However, although not completely clear, these complications seem to be linked most often to prolonged treatment, genetic variability, and predisposition to hypersensitivity. Data supporting the contraindication of nitrofurantoin for patients with a CrCl less than 60 mL/min are nonexistent. Well-designed clinical trials with urinary concentration information and clinical end points on patients with various degrees of renal impairment are much needed. Until such a study becomes available, the limited data available would support considering using this drug in patients with a CrCl of 40 mL/min or higher.


Hormonal changes and mood in the puerperium.
This investigation is an attempt to test the common supposition that postpartum emotional disturbance is related to hormone changes. A group of 27 normal pregnant women were assessed three times before delivery and sixteen times in the six weeks following delivery. During the first two interviews baseline data on personality and other personal variables were obtained. On each occasion blood was taken and three measures of clinical status and mood were completed. Plasma LH, FSH, total oestrogen and progesterone results are presented in detail and the results of prolactin assays mentioned more briefly. An attempt to correlate hormone findings and clinical findings is described. This failed to produce any strong evidence that hormones are related to mood at this time, although hormone changes were correlated weakly with a few specific symptoms. Some of the unexpected clinical findings and technical difficulties of the study are discussed, with special reference to possible further research in this area.


Artemia salina as test organism for assessment of acute toxicity of leachate water from landfills.
Artemia salina has, for the first time, been used as test organism for acute toxicity of leachate water from three landfills (the municipal landfills at Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in different ways in a pilot plan). Artemia can tolerate the high concentrations of chloride ions found in such waters. Large differences in toxicities were found, the leachate from Siauliai being the most toxic one. To increase the selectivity in the measurements, a fractionation was done by using ion exchange to separate ammonium/ammonia and metal ions from the leachate, and activated carbon adsorbents for organic pollutants. The influence of some metals and phenol compounds on the toxicity was investigated separately. It was found that most of the toxicity emanated from the ammonium/ammonia components in the leachate. However, there was also a significant contribution n from organic pollutants, other than phenol compounds, since separate experiments had in this latter case indicated negligible impact. The concentrations of metals were at a level, shown by separate experiments, where only small contribution to the toxicity could be expected.


Differences in Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at Burn Centers and Nonburn Centers.
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and Stevens-Johnson/TEN overlap syndrome (SJS/TEN) are severe exfoliative skin disorders resulting primarily from allergic drug reactions and sometimes from viral causes. Because of the significant epidermal loss in many of these patients, many of them end up receiving treatment at a burn center for expertise in the care of large wounds. Previous work on the treatment of this disease focused only on the differences in care of the same patients treated at nonburn centers and then transferred to burn centers. We wanted to explore whether patients had any differences in care or outcomes when they received definitive treatment at burn centers and nonburn centers. We queried the National Inpatient Sample database from 2016 for patients with SJS, SJS/TEN, and TEN diagnoses. We considered burn centers as those with greater than 10 burn transfers to their center and fewer than 5 burn transfers out of their center in a year. Multivariable logistic regression assessed factors associated with treatment at a burn center and mortality. Using the National Inpatient Sample, a total of 1164 patients were identified. These were divided into two groups, nonburn centers vs burn centers, and those groups were compared for demographic characteristics as well as variables in their hospital course and outcome. Patients treated at nonburn centers were more likely to have SJS and patients treated at burn centers were more likely to have both SJS/TEN and TEN. Demographics were similar between treatment locations, though African-Americans were more likely to be treated at a burn center. Burn centers had higher rates of patients with extreme severity and mortality risks and a longer length of stay. However, burn centers had similar actual mortality compared to nonburn centers. Patients treated at burn centers had higher charges and were more likely to be transferred to long-term care after their hospital stay. The majority of patients with exfoliative skin disorders are still treated at nonburn centers. Patients with SJS/TEN and TEN were more likely to be treated at a burn center. Patients treated at burn centers appear to have more severe disease but similar mortality to those treated at nonburn centers. Further study is needed to determine whether patients with these disorders do indeed benefit from transfer to a burn center.


Left atrial volume and function in patients with white-coat hypertension assessed by real-time three-dimensional echocardiography.
White-coat hypertension (WCH) is a disease based on the disparity of a patient's blood pressure measurements between the physician's office and the patient's home environment. The aim of the present study is to evaluate the left atrial (LA) volume and functions in WCH. In total, this study included 37 WCH (17 women, 20 men, mean age 48.4±5.7 years) and 30 healthy individuals (18 women, 20 men, mean age 47.9±7.5 years). All patients underwent real-time three-dimensional and comprehensive two-dimensional echocardiography (2DE) with tissue Doppler evaluation to estimate left atrial volumes and mechanical functions. LA diameters were significantly higher in the patients compared with the controls (37±2.8 vs. 35±3.1 mm, P=0.017). LA total systolic volume and LA maximal volume were significantly higher in the patients. (41.1±6.9 vs. 35.5±3.7 ml, P<0.001; 25.8±5.4 vs. 21.3±3.3 ml, P<0.001, respectively). LA volume before LA contraction and LA active stroke volume were significantly higher in the patients with WCH than in the normotensives (24.4±6.3 vs. 20.9±2 ml, P=0.002; 9.1±4.8 vs. 6.7±2.5 ml, P=0.007, respectively). Moreover, the LA expansion index was significantly higher in the patients with WCH than in the normotensives (178.7±53.6 vs. 155.3±36.3, P=0.037). However, the total emptying volume fraction of the LA was similar between the two groups. We showed that LA structural functions and volumes were increased in the WCH group. Although increased LA volume has been observed in many diseases, structural changes in LA may be accepted as an early sign for clinical cardiac remodeling in patients with WCH, suggesting the necessity of early intervention for preventing clinical cardiovascular disease.


Evaluation of real-world mobility in age-related macular degeneration.
Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures. In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11). AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients.


Albuterol-induced downregulation of Gsalpha accounts for pulmonary beta(2)-adrenoceptor desensitization in vivo.
The aim of the present study was to develop a chronic in vivo model of pulmonary beta(2)-adrenoceptor desensitization and to elucidate the nature and molecular basis of this state. Subcutaneous infusion of rats with albuterol for 7 days compromised the ability of albuterol, given acutely, to protect against acetylcholine-induced bronchoconstriction. The bronchoprotective effect of prostaglandin E(2), but not forskolin, was also impaired, indicating that the desensitization was heterologous and that the primary defect in signaling was upstream of adenylyl cyclase. beta(2)-Adrenoceptor density was reduced in lung membranes harvested from albuterol-treated animals, and this was associated with impaired albuterol-induced cyclic adenosine monophosphate (cAMP) accumulation and activation of cAMP-dependent protein kinase ex vivo. Gsalpha expression was reduced in the lung and tracheae of albuterol-treated rats, and cholera toxin-induced cAMP accumulation was blunted. Chronic treatment of rats with albuterol also increased cAMP phosphodiesterase activity and G protein-coupled receptor kinase-2, but the extent to which these events contributed to beta(2)-adrenoceptor desensitization was unclear given that forskolin was active in both groups of animals and that desensitization was heterologous. Collectively, these results indicate that albuterol effects heterologous desensitization of pulmonary Gs-coupled receptors in this model, with downregulation of Gsalpha representing a primary molecular etiology.


Automatic sleep scoring in normals and in individuals with neurodegenerative disorders according to new international sleep scoring criteria.
The aim of this study was to develop a fully automatic sleep scoring algorithm on the basis of a reproduction of new international sleep scoring criteria from the American Academy of Sleep Medicine. A biomedical signal processing algorithm was developed, allowing for automatic sleep depth quantification of routine polysomnographic recordings through feature extraction, supervised probabilistic Bayesian classification, and heuristic rule-based smoothing. The performance of the algorithm was tested using 28 manually classified day-night polysomnograms from 18 normal subjects and 10 patients with Parkinson disease or multiple system atrophy. This led to quantification of automatic versus manual epoch-by-epoch agreement rates for both normals and abnormals. Resulting average agreement rates were 87.7% (Cohen's Kappa: 0.79) and 68.2% (Cohen's Kappa: 0.26) in the normal and abnormal group, respectively. Based on an observed reliability of the manual scorer of 92.5% (Cohen's Kappa: 0.87) in the normal group and 85.3% (Cohen's Kappa: 0.73) in the abnormal group, this study concluded that although the developed algorithm was capable of scoring normal sleep with an accuracy around the manual interscorer reliability, it failed in accurately scoring abnormal sleep as encountered for the Parkinson disease/multiple system atrophy patients.


Hidden histories of gene flow in highland birds revealed with genomic markers.
Genomic studies are revealing that divergence and speciation are marked by gene flow, but it is not clear whether gene flow has played a prominent role during the generation of biodiversity in species-rich regions of the world where vicariance is assumed to be the principal mode by which new species form. We revisit a well-studied organismal system in the Mexican Highlands, Aphelocoma jays, to test for gene flow among Mexican sierras. Prior results from mitochondrial DNA (mtDNA) largely conformed to the standard model of allopatric divergence, although there was also evidence for more obscure histories of gene flow in a small sample of nuclear markers. We tested for these 'hidden histories' using genomic markers known as ultraconserved elements (UCEs) in concert with phylogenies, clustering algorithms and newer introgression tests specifically designed to detect ancient gene flow (e.g. ABBA/BABA tests). Results based on 4303 UCE loci and 2500 informative SNPs are consistent with varying degrees of gene flow among highland areas. In some cases, gene flow has been extensive and recent (although perhaps not ongoing today), whereas in other cases there is only a trace signature of ancient gene flow among species that diverged as long as 5 million years ago. These results show how a species complex thought to be a model for vicariance can reveal a more reticulate history when a broader portion of the genome is queried. As more organisms are studied with genomic data, we predict that speciation-with-bouts-of-gene-flow will turn out to be a common mode of speciation.


Use of NIDSEC-compliant CIS in community-based nursing-directed prenatal care to determine support of Nursing Minimum Data Set objectives.
If the Nursing Minimum Data Set elements, specifically the nursing care elements, are included in a clinical information system, nursing will be able to measure outcomes and contributions to both healthcare and nursing to build knowledge using clinical data. The purpose of the reported study was to determine whether a Nursing Information and Data Set Evaluation Center-compliant clinical information system using the Omaha System could support the Nursing Minimum Data Set goal to describe nursing care in a community health setting. The secondary data set analysis was conducted. The findings showed that although the clinical information system was compliant with the standard, used a recognized American Nurses Association nursing vocabulary, and supported the collection of the Nursing Minimum Data Set, the data were not sufficient to address the purposes of the Nursing Minimum Data Set. The implications for nursing research and clinical practice are outlined.


Does one's sense of coherence change after an acute myocardial infarction? A two-year longitudinal study in Sweden.
The aim of this study was to assess changes in the sense of coherence of patients who had suffered their first myocardial infarction. Out of 100 patients at the start of the study, these changes were evaluated in 66 men and 18 women aged 36-70 years. Generally, the sense of coherence was found to be stable among the whole group, but there were significant individual variations in its development in some of the participants over the following years. Even the individuals with an initally high sense of coherence could experience a decrease in its level. The changes that were found in the men can be explained by their marital status, level of treatment satisfaction, disease perception/quality of life, physical limitation, and alcohol intake and/or tobacco use at the baseline. An unexpected finding was that the single men with an initially high sense of coherence experienced a decreased level over time. In order to maintain or increase patients' sense of coherence, it is important for nurses to help them identify their risk factors and to provide conditions for individualized cardiac rehabilitation in order to avoid another myocardial infarction.


Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome.
Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic disorders. Among the identified causes of HUS are infections, particularly infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement disorders, and disorders interfering with the degradation of von Willebrand factor (VWF). Other causes for atypical HUS include the cobalamin metabolism; pregnancy/hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP); drugs; and other disorders (e.g., systemic diseases appearing as HUS, such as systemic lupus erythematosus and rejection after transplantation). The group not related to STEC is often also called atypical HUS. Most of the occurrences of infectious HUS have only one episode. Recurrent episodes (recurrent HUS) have strong relationships to diseases of the complement system. In these two subgroups the prognosis is poor, with severe renal insufficiency, together with the need for renal replacement therapy. Severe arterial hypertension is common. Treatment options are limited. To better define this group of patients, the European Society for Pediatric Nephrology supported an initiative to develop a European HUS registry. In this registry, 167 patients were acquired; 73 were female (43.8%). The year of onset of the disease ranged from 1974 to 2005. The prevalence of atypical HUS/recurrent HUS can be calculated as 3.3 per million child population (< 18 years). Underlying disorders included factor H, factor I, MCP-1, pneumococci, and von Willebrand factor disturbances. In 33 patients at least one renal transplantation was performed (total, 55 kidneys); 18% were successful and 73% demonstrated recurrence or thrombosis. Treatment options were plasma substitution or plasmapheresis. Despite continued efforts, transplantation is not recommended at present for these patients. Living-related transplantation should be abandoned. New therapeutic strategies are urgently needed.


Sensorimotor locus of the buildup activity in monkey lateral intraparietal area neurons.
A study in 2002 using a random-dot motion-discrimination paradigm showed that an information accumulation model with a threshold-crossing mechanism can account for activity of the lateral intraparietal area (LIP) neurons. Here, mathematical techniques were applied to the same dataset to quantitatively address the sensory versus motor representation of the neuronal activity during the time course of a trial. A technique based on Signal Detection Theory was applied to provide indices to quantify how neuronal firing activity is responsible for encoding the stimulus or selecting the response at the behavioral level. Additionally, a statistical model based on Poisson regression was used to provide an orthogonal decomposition of the neural activity into stimulus, response, and stimulus-response mapping components. The temporal dynamics of the sensorimotor locus of the LIP activity indicated that there is no stimulus-response mapping-specific neuronal firing activity throughout a trial; the neural activity toward the saccadic onset reflects the development of the motor representation, and the neural activity in the beginning of a trial contains little, if any, information about the sensory representation. Sensorimotor analysis on individual neurons also showed that the neuronal activation, as a population, represent pending saccadic direction and carry little information about the direction of the motion stimulus.


Autoregulation of endogenous epinephrine release via presynaptic adrenoceptors in the rat hypothalamic slice.
High-K+ (30 mM)-evoked release of endogenous epinephrine in hypothalamic slices from three rats in the presence of tetrodotoxin, 3 X 10(-7) M, was measured by high-performance liquid chromatography with an electrochemical detector. Spontaneous and evoked release of epinephrine was markedly reduced, when rats were pretreated with 2,3-dichloro-alpha-methylbenzylamine, an inhibitor of phenylethanolamine N-methyltransferase, the enzyme catalyzing the formation of epinephrine from norepinephrine, 80 mg/kg i.p., before decapitation. The amount of epinephrine released during the resting state was lower by a factor of approximately 2 orders than that of norepinephrine and dopamine but was consistently higher than the limit of the sensitivity of this assay system, 0.1 to 0.3 pmol. The evoked release of epinephrine was Ca++ dependent. Isoproterenol, 10(-8) M to 10(-7) M, dose dependently increased this parameter. I-Propranolol, 3 X 10(-8) M, shifted the dose-effect curve of isoproterenol to the right. Atenolol, 10(-6) M, and butoxamine, 3 X 10(-8) M, beta-1 and beta-2 antagonists, respectively, antagonized the action of isoproterenol, 3 X 10(-8) M. Tazolol, 3 X 10(-7) and 10(-6) M, a beta-1 agonist, and salbutamol, 10(-8) and 3 X 10(-8) M, a beta-2 agonist, dose dependently increased the evoked release of epinephrine. I-Propranolol, 3 X 10(-7) M and 3 X 10(-6) M alone, dose dependently decreased this parameter, but the d-isomer produced no effect. Clonidine, 10(-8) and 10(-7) M, an alpha-2 agonist, dose dependently decreased the parameter, and this decrease was antagonized by yohimbine, 10(-6) M, an alpha-2 antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)


Construction of supramolecular organogels and hydrogels from crown ether based unsymmetric bolaamphiphiles.
A bolaamphiphilic low-molecular-weight gelator based on crown ether, which could self-assemble into organogels and hydrogels, was prepared. The contribution of each part of the structure to the gelation property was investigated by designing a series of analogues. A simple framework (crown ether-hydrophobic linkage-ammonium salt) was proposed.


A pilot study of the prevalence of herpes genitalis among selected groups of patients seeking care in a family practice center.
Herpes genitalis is typically studied in patient panels identified at specialized sexually transmitted disease clinics or with information obtained from herpes self-help groups. This article reports the results of a descriptive pilot study of the prevalence of herpes genitalis in family practice. The feasibility of obtaining psychosexual information on sexually transmitted diseases from more than 600 patients from five family practice practices was assessed. These initial data show that in the family practices participating in this study: 1) genital herpes is a low prevalence disease; 2) psychosocial adjustment to the disease among infected persons is usually reported as good, apart from sexual effects; and 3) close to 30% of the study population reported having prior sexually transmitted diseases. Problems involved in generalizing the results of this research and the limitations of conducting collaborative clinical research in family practice settings are reviewed.


Improving Adherence to Practice Guidelines for Anticoagulation in Patients Receiving Neuraxial Anesthesia Using an Electronic Order Entry Alert System.
Epidural analgesia is frequently used to alleviate postoperative pain. Though rare, epidural hematoma continues to be a feared complication of neuraxial analgesia. The risk of epidural hematoma is likely increased when certain regimens are used for prophylaxis/treatment of venous thromboembolism. To help decrease the risk, we developed an alert in our electronic medical record to assist providers with adherence to published guidelines addressing neuraxial analgesia and anticoagulation. Patient data were collected retrospectively 3 months before and 3 months after the initiation of the computerized alert to assess the effectiveness of the alert. Patients were included if they had a procedure code associated with epidural analgesia. Pregnant patients and children were excluded. Type and frequency of antithrombotic medications were recorded for comparison to published practice guidelines. Using Poisson regression to describe the data, patients with epidurals after the best practice alert observed a 61% decrease in the expected number of days of exposure to inappropriate doses of anticoagulation versus patients treated before implementation of the alert. Unapproved antithrombotic administration was significantly reduced after initiation of the alert system. This simple electronic alert was found to have a protective effect for patients receiving both anticoagulation and epidural analgesia.


Development of the antibody response in acute HIV-1 infection.
Cytotoxic T lymphocytes have been shown to reduce viraemia during acute HIV-1 infection; however the role of neutralizing antibodies in this process is unclear. One confounding factor may be artefacts introduced by viral culture. To assess the development of autologous neutralizing and non-neutralizing antibodies following acute HIV-1 infection using recombinant viruses with envelopes amplified directly from patient peripheral blood mononuclear cells, thereby avoiding in vitro selection. Disease progression in four homosexual men was monitored from acute infection for up to 2.5 years, in the absence of antiretroviral therapy. Antibodies to viral envelope protein were quantified by enzyme-linked immunosorbent assay. Development of neutralizing antibodies was monitored using a quantitative infectivity reduction assay, sequential serum, recombinant viruses and target cells with defined receptor expression. The time to development of neutralizing antibodies after onset of symptoms was 3, 5, 7 and 16 months in the four patients. There was no correlation between development of neutralizing antibodies and the resolution of viraemia in any of the patients. However, antibodies to the envelope were detectable as early as 2 weeks after onset of symptoms. Neutralizing antibodies do not contribute to the control of viraemia in acute HIV-1 infection. However, antibodies to the envelope could be detected at the time of reduction in plasma viraemia and so other effector functions of antibodies may play a role in viral clearance.


Levofloxacin Versus Ciprofloxacin-Based Prophylaxis during the Pre-Engraftment Phase in Allogeneic Hematopoietic Stem Cell Transplant Pediatric Recipients: A Single-Center Retrospective Matched Analysis.
Infectious complications are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Antibacterial prophylaxis in pediatric cancer patients is a controversial issue. Our study compared the outcomes of levofloxacin versus ciprofloxacin prophylaxis in allogeneic HSCT pediatric recipients treated for hematological malignancies. A total of 120 patients received levofloxacin prophylaxis, and 60 patients received ciprofloxacin prophylaxis. Baseline characteristics such as age, gender, primary diagnosis, type of conditioning, donor type, stem cell source, and supportive care of the patients were similar, and duration of antibiotics prophylaxis was similar. Both prophylaxis regimens demonstrated the same efficacy on the risk of febrile neutropenia and severe complications such as sepsis, the same rate of overall mortality, hospital readmission, and length of hospital stay. Levofloxacin prophylaxis was associated with significantly lower cumulative antibiotic exposure. The median of Gram-positive infection-related antibiotic days was 10 days in the levofloxacin group versus 25 days in the ciprofloxacin group (p < 0.0001). The median of Gram-negative infection-related antibiotics was 10 days in the levofloxacin group compared with 20 days in the ciprofloxacin group (p < 0.0001). The number of days with body temperature ≥38 °C was significantly less in the levofloxacin group (p < 0.001).


THE VOLUME OF SOLITARY PARATHYROID ADENOMA IS RELATED TO PREOPERATIVE PTH AND 25OH-D3, BUT NOT TO CALCIUM LEVELS.
To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.


Cyclotide synthesis and supply: from plant to bioprocess.
Cyclotides are disulfide-rich miniproteins with a circular backbone and a knotted arrangement ofdisulfide bonds. Because these plant-derived peptides are resistant to degradation and exhibit a diverse range of bioactivity they have become important agronomic and industrial objectives. They belong to a group of compounds with low market volume and high price that are poorly processed by microorganisms, are too complex for economic chemical synthesis, and thus are valuable candidates for the synthesis in plant cell bioprocesses. This review highlights current research aimed at production routes of cyclotides in Oldenlandia affinis plantlets and cell cultures, and summarizes recent advances in bioprocessing aspects, with particular emphasis on the development of suitable bioreactor configurations for plant cell culture-based processes, the optimization of culture environments as a powerful means to improve yields, bioreactor operational modes, and trends in protein recovery.


Immunity and health of two wild marine fishes naturally exposed to anthropogenic pollution.
There are increasing global concerns of the alarming pollution impacts on marine life, thus it is becoming essential to generate reliable tools to monitor and understand the effects of these impacts on aquatic organisms. We performed a field study assessing how exposure to anthropogenic pollution impacts immunological and health-state parameters and parasite infection of a wild marine fish, the Brazilian sandperch Pinguipes brasilianus. Then we compared this information to previously published data of a sympatric species, the Patagonian rockfish Sebastes oculatus inhabiting the same polluted and pristine areas. The field study revealed that exposed P. brasilianus showed chronic stress, poor immune condition and higher prevalence and abundance of acanthocephalan parasites. By comparing these former results with already published in S. oculatus, we concluded that, although both species exhibited physiological alterations associate to inhabiting sites exposed to pollution, their specific immunological and health-state responses differed. Our results demonstrate that Patagonian reef-fish assemblages inhabiting sites exposed to pollutant are being affected in their immune and heath condition, which could potentially result in higher susceptibility to disease and in turn population decline. These findings highlight the necessity of more studies incorporating interspecific comparisons to assess variation in fish susceptibility in an ecoimmunotoxicological context and get a more profound understanding of anthropogenic impacts on wildlife.


Maintenance of meiotic arrest and the induction of oocyte maturation in mouse oocyte-granulosa cell complexes developed in vitro from preantral follicles.
During the development of oocyte-granulosa cell complexes from preantral follicles in vitro, oocytes grow and acquire competence to undergo germinal vesicle breakdown (GVB). In the culture system used here, GVB-competent oocytes were maintained in meiotic arrest solely by endogenous physiological mechanisms of the granulosa cells without supplementation with meiosis-arresting substances. Addition of mycophenolic acid, an inhibitor of inosine monophosphate (IMP) dehydrogenase, induced GVB in about 70% of the GVB-competent oocytes grown in vitro. The mechanism for meiotic arrest in this system is, therefore, similar to that for arrest in vivo insofar as it requires the participation of the IMP dehydrogenase pathway. Rp-cyclic adenosine monophosphothioate, a membrane-permeable antagonist to cAMP, induced GVB by about 30% of the competent oocytes. Cyclic AMP-dependent pathways, therefore, participate in the physiological mechanism by which mouse granulosa cells maintain meiotic arrest. Complexes were grown for 10 days in medium containing 0, 1, 5, or 10 ng/ml FSH, were stimulated with either 1 microgram/ml FSH or LH, and were assessed for GVB and cumulus expansion. GVB was stimulated by FSH whether or not the complexes were grown in medium containing FSH, but LH or hCG induced GVB only when the complexes were grown in medium containing FSH. Cumulus expansion occurred in response to either FSH or LH only when complexes were grown in medium containing FSH. FSH, therefore, promotes the differentiation of granulosa cells from preantral follicles in vitro so that LH can stimulate GVB and cumulus expansion.


A genome-wide screen reveals the involvement of enterobactin-mediated iron acquisition in Escherichia coli survival during copper stress.
Copper (Cu) is a key transition metal that is involved in many important biological processes in a cell. Cu is also utilized by the immune system to hamper pathogen growth during infection. However, genome-level knowledge on the mechanisms involved in adaptation to Cu stress is limited. Here, we report the results of a genome-wide reverse genetic screen for Cu-responsive phenotypes in Escherichia coli. Our screen has identified novel genes involved in adaptation to Cu stress in E. coli. We detected multiple genes involved in the biosynthesis and uptake of enterobactin, a siderophore utilized for high-affinity TonB-dependent acquisition of iron (Fe), as critical players in survival under Cu intoxication. We demonstrated the specificity of Cu-dependent killing by chelation of Cu and by genetic complementation of tonB. Notably, TonB is involved in protection from Cu in both laboratory and uropathogenic strains of E. coli. Cu stress leads to increased expression of the genes involved in Fe uptake, indicating that Fur regulon is derepressed during exposure to excess Cu. Trace element analyses revealed that Fe homeostasis is dysregulated during Cu stress. Taken together, our data supports a model in which lack of enterobactin-dependent Fe uptake leads to exacerbation of Cu toxicity, and elucidates the intricate connection between the homeostasis of Cu and Fe in a bacterial cell.


Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI-measured liver iron content.
Using liver magnetic resonance imaging (R2-MRI) to quantify liver iron content (LIC), we conducted a prospective cohort study to determine the association between iron overload and adult allogeneic hematopoietic cell transplantation (HCT) outcomes. Patients received pretransplant ferritin measurements; patients with ferritin >500 ng/mL underwent R2-MRI. Patients were defined as no iron overload (N = 28) and iron overload (LIC >1.8 mg/g; N = 60). Median LIC in the iron-overload group was 4.3 mg/g (range, 1.9-25.4). There was no difference in the 1-year probability of overall survival, nonrelapse mortality, relapse, acute or chronic graft-versus-host disease, organ failure, infections, or hepatic veno-occlusive disease between groups. We also found no difference in the cumulative incidence of a composite end point of nonrelapse mortality, any infection, organ failure, or hepatic veno-occlusive disease (1-year cumulative incidence, 71% vs 80%; P = .44). In multivariate analyses, iron-overload status did not impact risks of overall mortality (relative risk = 2.3; 95% confidence interval, 0.9-5.9; P = .08). In conclusion, we found no association between pretransplant iron overload and allogeneic HCT outcomes. Future studies in this population should use LIC to define iron overload instead of ferritin.


Staphylococcus aureus lipotechoic acid induces differential expression of bovine serum amyloid A3 (SAA3) by mammary epithelial cells: Implications for early diagnosis of mastitis.
Mastitis is one of the most costly diseases of agriculturally important animals and is a common problem for lactating cows. Current methods used to detect clinical and especially subclinical mastitis are either inadequate or problematic. Pathogens such as the gram-positive bacterium Staphylococcus aureus or the gram-negative bacterium Escherichia coli typically cause mastitis. E. coli induces clinical mastitis, whereas, S. aureus causes a subclinical, chronic infection of the mammary gland. In this study we report the differential expression and secretion of mammary-derived serum amyloid A3 (SAA3) by bovine mammary epithelial cells following stimulation with the S. aureus cell wall component, lipotechoic acid (LTA). Two-dimensional immunoblot analyses confirmed that bovine SAA3 is the predominant SAA isoform produced by LTA stimulated mammary epithelial cells. Our previous study showed that bovine SAA3 is also differentially expressed in response to the gram-negative bacterial endotoxin lipopolysaccharide. Collectively, these data indicate that the local production of SAA3 by mammary epithelial cells in response to either gram-positive or gram-negative bacterial components may provide a sensitive indicator for early detection and treatment of mastitis in vivo, minimizing chronic cases of infection, the spread of mastitis to other animals, and economic losses.


The View from the Benches: Scientists' Perspectives on the Uses and Governance of Human Gene-Editing Research.
The advent of human gene editing has stimulated international interest in how best to govern this research. However, research on stakeholder views has neglected scientists themselves. We surveyed 212 scientists who use gene editing in their work. Questions captured views on oversight and use of somatic and germline human gene editing for treatment, prevention, and enhancement. More respondents were supportive of somatic than germline editing, and more supported gene editing for treatment compared to prevention. Few supported its use for enhancement. When presented with specific conditions, levels of support for somatic editing differed by type of condition. Almost all respondents said scientists and national government representatives should be involved in oversight, but only 28% said scientists are best positioned to oversee gene-editing research. These results can inform the development of sound approaches to research governance, demonstrating the importance of identifying specific gene-editing uses when considering oversight.


High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and meta-analysis.
To systematically review evidence comparing the effect of low-dose versus high-dose ACE inhibitors (ACEIs) on all-cause and cardiovascular mortality and hospitalisation, functional capacity and side effects in patients with heart failure (HF). We searched PubMed, Embase, Cochrane CENTRAL and LILACS up to January 2019. We included randomised controlled trials (RCTs) comparing low-dose versus high-dose ACEIs in adults with HF with reduced left ventricular ejection fraction (HFrEF). Study selection and data extraction were performed by two independent reviewers. Risk of bias was assessed with RoB 2.0, and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We conducted random effects meta-analysis and trial sequential analysis. We included eight RCTs (5829 patients with HF). In comparison with low-dose ACEIs, high-dose ACEIs showed a non-significant effect on all-cause mortality (8 RCTs, n=5828, relative risk (RR) 0.95, 95% CI 0.88 to 1.02; moderate quality of evidence), cardiovascular mortality (6 RCTs, n=4048, RR 0.93, 95% CI 0.85 to 1.01; moderate quality of evidence), all-cause hospitalisation (5 RCTs, n=5394, RR 0.95, 95% CI 0.82 to 1.10; moderate quality of evidence) and cardiovascular hospitalisation (4 RCTs, n=5242, RR 0.98, 95% CI 0.83 to 1.17; low quality of evidence). High-dose ACEI increased functional capacity (4 studies, n=555, standardised mean difference 0.38, 95% CI 0.20 to 0.55; low quality of evidence) and the risk of hypotension (4 RCTs, n=3783, RR 1.64, 95% CI 1.30 to 2.05; moderate quality of evidence). High-dose ACEI had no effect on dizziness (3 RCTs, n=4994, RR 1.37, 95% CI 0.97 to 1.93; low quality of evidence), but decreased the risk of cough (4 RCTs, n=5146, RR 0.85, 95% CI 0.73 to 0.98; moderate quality of evidence). The magnitude of benefit of using high dose versus low to intermediate doses of ACEIs might be less than traditionally suggested in clinical guidelines. These findings might help clinicians address the complex task of HF management in a more rational and timely fashion, saving efforts to implement strategies with the greatest net clinical benefit.


Development of molecular precursors for deposition of indium sulphide thin film electrodes for photoelectrochemical applications.
Symmetrical and unsymmetrical dithiocarbamato pyridine solvated and non-solvated complexes of indium(III) with the general formula [In(S2CNRR')3]·n(py) [where py = pyridine; R,R' = Cy, n = 2 (1); R,R' = (i)Pr, n = 1.5 (2); NRR' = Pip, n = 0.5 (3) and R = Bz, R' = Me, n = 0 (4)] have been synthesized. The compositions, structures and properties of these complexes have been studied by means of microanalysis, IR and (1)H-NMR spectroscopy, X-ray single crystal and thermogravimetric (TG/DTG) analyses. The applicability of these complexes as single source precursors (SSPs) for the deposition of β-In2S3 thin films on fluorine-doped SnO2 (FTO) coated conducting glass substrates by aerosol-assisted chemical vapour deposition (AACVD) at temperatures of 300, 350 and 400 °C is studied. All films have been characterized by powder X-ray diffraction (PXRD) and energy dispersive X-ray analysis (EDX) for the detection of phase and stoichiometry of the deposit. Scanning electron microscopy (SEM) studies reveal that precursors (1)-(4), irrespective of different metal ligand design, generate comparable morphologies of β-In2S3 thin films at different temperatures. Direct band gap energies of 2.2 eV have been estimated from the UV-vis spectroscopy for the β-In2S3 films fabricated from precursors (1) and (4). The photoelectrochemical (PEC) properties of β-In2S3 were confirmed by recording the current-voltage plots under light and dark conditions. The plots showed anodic photocurrent densities of 1.25 and 0.65 mA cm(-2) at 0.23 V vs. Ag/AgCl for the β-In2S3 films made at 400 and 350 °C from the precursors (1) and (4), respectively. The photoelectrochemical performance indicates that the newly synthesised precursors are highly useful in fabricating β-In2S3 electrodes for solar energy harvesting and optoelectronic application.


Work stress of primary care physicians in the US, UK and German health care systems.
Work-related stress among physicians has been an issue of growing concern in recent years. How and why this may vary between different health care systems remains poorly understood. Using an established theoretical model (effort-reward imbalance), this study analyses levels of work stress among primary care physicians (PCPs) in three different health care systems, the United States, the United Kingdom and Germany. Whether professional autonomy and specific features of the work environment are associated with work stress and account for possible country differences are examined. Data are derived from self-administered questionnaires obtained from 640 randomly sampled physicians recruited for an international comparative study of medical decision making conducted from 2005 to 2007. Results demonstrate country-specific differences in work stress with the highest level in Germany, intermediate level in the US and lowest level among UK physicians. A negative correlation between professional autonomy and work stress is observed in all three countries, but neither this association nor features of the work environment account for the observed country differences. Whether there will be adequate numbers of PCPs, or even a field of primary care in the future, is of increasing concern in several countries. To the extent that work-related stress contributes to this, identification of its organizational correlates in different health care systems may offer opportunities for remedial interventions.


Functionalized mesoporous SBA-15 silica: recent trends and catalytic applications.
The development of advanced materials for heterogeneous catalytic applications requires fine control over the synthesis and structural parameters of the active site. Mesoporous silica materials have attracted increasing attention to be considered as an important class of nanostructured support materials in heterogeneous catalysis. Their large surface area, well-defined porous architecture and ability to incorporate metal atoms within the mesopores lead them to be a promising support material for designing a variety of different catalysts. In particular, SBA-15 mesoporous silica has its broad applicability in catalysis because of its comparatively thicker walls leading to higher thermal and mechanical stability. In this review article, various strategies to functionalize SBA-15 mesoporous silica have been reviewed with a view to evaluating its efficacy in different catalytic transformation reactions. Special attention has been given to the molecular engineering of the silica surface, within the framework and within the hexagonal mesoporous channels for anchoring metal oxides, single-site species and metal nanoparticles (NPs) serving as catalytically active sites.


[Correlation of E2a-pbx1 expression level with clinical characteristics and early response to treatment in children with acute lymphoblastic leukemia].
This study purposed to investigate the correlation of expression level of e2a-pbx1 (immunoglobulin enhancer binding factor-Pre-B leukemia) with clinical characteristics and early response to treatment in children patients with acute lymphoblastic leukemia (ALL). The expression level of e2a-pbx1 at primary diagnosis in 45 children with ALL, and on day 33 after induction of remission in 23 children with ALL were detected by real-time quantitative polymerase chain reaction (RQ-PCR). The corelation of e2a-pbx1 expression level at primary diagnosis, MRD level with clinical characteristics and early response to treatment were all observed and explored. The expression level of e2a-pbx1 and clinical characteristics at primary diagnosis were compared between MRD negative and MRD positive patients. The results showed that the expression level of e2a-pbx1 was correlated with the blast percentage in peripheral blood at primary diagnosis. The MRD level at day 33 after induction of remission in 23 children were not related to the expression level of e2a-pbx1 at primary diagnosis and the clinical characteristics. The expression level of e2a-pbx1 at primary diagnosis in MRD positive patients was higher than that in MRD negative patients, while their age was significantly lower than that of patients with MRD negative. The blast percentage in peripheral blood at diagnosis of patients with presenting leukocyte count < 25 x 10(9)/L was significantly lower than that of patients with presenting leukocyte count >or= 25 x 10(9)/L, while the platelet count was higher. It is concluded that the expression level of e2a-pbx1 at primary diagnosis indicates the load of tumor in patients. In patients whose MRD were positive, the expression level of e2a-pbx1 at primary diagnosis is high and their age is young. The platelet count is low in the patients with high load of tumor at primary diagnosis.


The relationship of intimate partner aggression to head injury, executive functioning, and intelligence.
Measures of head injury, executive functioning, and intelligence were given to a community sample composed of 102 male perpetrators of intimate partner aggression (IPA) and 62 nonaggressive men. A history of head injury and lower mean score on a measure of verbal intelligence were associated with the frequency of male-perpetrated physical IPA as reported by male perpetrators and their female partners. Lower mean scores on a measure of verbal intelligence also predicted frequency of psychological IPA perpetration. Using the perpetrator subtypes outlined by Holtzworth-Munroe et al. (2000), analyses revealed that compared with other groups, the most severely aggressive subtypes (i.e., borderline-dysphoric and generally violent-antisocial) were the most likely to report a history of head injury and to have significantly lower mean scores on a neuropsychological test of verbal intelligence. The possible role of neuropsychological factors in IPA perpetration and implications for prevention and intervention programs are discussed.


Trauma patients: an analysis of rural ambulance trip reports.
This study summarizes all 2,550 trauma-related rural ambulance trip reports filed for the period January 1 through December 31, 1991 from the 12 rural counties surrounding Augusta, Georgia. There were 13.1 trauma-related ambulance runs per 1,000 population. Nearly one third of all rural ambulance runs are trauma related. Severe trauma constituted less than 8.0% of trauma cases. Forty-one cases died at the scene and 19 additional cases died from any cause within 30 days of transport. The mean response time was 8.5 minutes and in 90% of all rural trauma runs the ambulance arrived in 17 minutes or less. Only 51.5% of runs had a rural hospital as a destination, 14.2% went directly to a trauma center, and nearly 20% to another urban hospital. Of the 71 severe trauma cases received by ambulance, rural hospitals transferred out only 13 cases, most of these to the regional trauma center. Of the 47 trauma cases transferred to the trauma center, 33 were not severe.


Dependence of guanidine sensitivity of poliovirus replication on the concentration of monovalent cations in the culture medium.
An earlier suggestion that guanidine may inhibit picornavirus replication by interfering with a monovalent cation-mediated event was tested by determining the effect of varying monovalent cation concentration in isotonic medium on the sensitivity of poliovirus replication in HeLa cells to 0.2 mM-guanidine. Lowering [Na+] in the medium to 50 mM had no effect on virus replication. It was found that the degree of inhibition of virus replication by 0.2 mM-guanidine was inversely related to [Na+] in the medium: 99.8%, 99.1%, 38% and 0% inhibition in the presence of 50, 75, 100 and 145 mM-Na+ respectively. Likewise, guanidine uptake by HeLa cells was also inversely related to [Na+] in the medium. On the other hand, lowering medium [Na+] to 50 or 75 mM resulted in reduced intracellular [Na+] and [K+]. The increased sensitivity of virus replication to guanidine in the presence of low Na+ medium could be abolished with excess K+ in such medium. Excess K+ in low Na+ medium restored intracellular [Na+] and reduced guanidine uptake. Thus, the increased sensitivity of poliovirus replication to guanidine in the presence of low Na+ medium correlated with reduced intracellular [Na+] and [K+] and elevated guanidine uptake.


[New clinical forms and diagnosis of ophthalmic chlamydiosis].
The paper deals with new clinical forms of ophthalmoclamidiosis involving lesions to the choroids, retina, optic nerve and cornea. Uveitis and scleritis were found in 73.5% and 26.5%, respectively. Iridocyclitis and paneveitis prevailed in cases of uveitis. Forty-two patients, aged 3 to 53, were followed up. Bilateral ocular lesions were registered in 67% of them. The progression, clinical course and outcomes of the disease were investigated by using the up-to-date laboratory-and-immunologic methods. Direct immunofluorescence and polymerase chain reaction, when used alongside with serological examinations, were found to be most informative. A combination of ophthalmoclamidiosis with urogenital pathologies was registered in 76% of patients.


A research agenda to support the development and implementation of genomics-based clinical informatics tools and resources.
The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled "Developing a Clinical Genomic Informatics Research Agenda". The meeting's goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings. Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting's goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy. Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address. Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them.


Induction of stable chimerism and elimination of graft-versus-host disease by depletion of T lymphocytes from bone marrow using immunomagnetic beads.
The goal of transplantation is the induction of immunologic tolerance. At present, nonspecific immunosuppression is used to prevent graft rejection and, commonly, graft-versus-host disease (GVHD). Nevertheless, nonspecific immunosuppressive therapy is frequently complicated by infection, malignant tumors, and drug toxicity. In order to examine whether hematopoietic chimerism can be used to induce specific allograft tolerance, we have reconstituted lethally irradiated Lewis rats with ACI bone marrow that has been depleted of T cells with use of immunomagnetic beads. This technique consists of binding OX-19, a mouse anti-rat pan-T lymphocyte monoclonal antibody, to magnetic polymer beads. Mixing of bone marrow or splenocytes with the bead/OX-19 complexes, followed by magnetic separation, results in significant depletion of T cells with minimal nonspecific cell loss. Immunomagnetic T-cell depletion of bone marrow, followed by reconstitution of a lethally irradiated host, allows for the development of stable, mixed hematopoietic chimerae without evidence of GVHD. These hosts are immunocompetent by clinical criteria. Recipients of untreated donor bone marrow that did or did not receive nonspecific immunosuppression demonstrated varying degrees of GVHD and reduced survival. The ability to rapidly and simply deplete T lymphocytes from bone marrow and produce stable, immunocompetent hematopoietic chimerae without GVHD may be an important method for tolerance induction to vascularized allografts.


Tethered Cord and Anorectal Malformations: A Case Series.
The clinical manifestation of a stretched low-lying cone (LLC) is represented by the tethered cord syndrome (TCS) with cutaneous, urologic, neurologic, and orthopaedic dysfunctions. TC is frequently found in patients with anorectal malformations (ARMs). The aim of our article is to report a series of patients affected by LLC and ARMs and evaluate their management and long-term follow-up results. We performed a retrospective analysis over a period of 15 years including patients with ARM and TC and excluding those with severe polymalformations. We collected information related to the types of malformations and demographic data. We analyzed their management (perinatal protocol, radiological investigations, surgery, and multidisciplinary follow-up). QOL was assessed through the International Classification of Functioning, Disability, and Health for Children and Youth (ICF-CY). Thirty-three patients among 210 ARM cases had TC (16%). Eleven of them underwent neurosurgery. One patient had retethering; out of 11 patients, 4 remained stable and 6 improved after surgery (UDS normalization and resolution of symptoms). At a mean follow-up of 10 years, four patients were on clean intermittent catheterization and five on the Peristeen transanal irrigation. The majority of patients were defined as 3 (from 1-bad to 5-excellent) for their physical and mental state. The use of MRI is considered to complete the ARM screening in detecting TC. The multidisciplinary approach is crucial and helps in defining the management of patients. In fact, it is not clear how the features of ARM and TC affect each other. The selection of cases for surgery should take into account the critical elements.


Global mortality trends and patterns in older women.
To describe mortality patterns in women older than 50 years in light of the growth, seen in almost all countries, in the absolute number of females in this age group and in the proportion of the female population comprising older women. National death record data and World Health Organization estimates of life expectancy and causes of death in women older than 50 years were analysed. Projections of trends in mortality, by cause, at older ages were also made. In both developed and developing countries, the leading causes of death among older women were cardiovascular diseases and cancers. In countries with death registration data, cardiovascular and (to a lesser extent) cancer mortality appears to have declined in older women in recent decades and this decline has resulted in improved life expectancy at age 50. If these trends continue, deaths in older women are still expected to increase in number because of population growth and ageing. Noncommunicable diseases, especially cardiovascular diseases and cancers, are expected to cause an increasing share of women's deaths in low- and middle-income countries owing to the ageing of the population and to reductions in child and maternal deaths. Health systems must adjust accordingly, perhaps by drawing on lessons from high-income countries that have succeeded in reducing mortality from noncommunicable diseases.


Practices and Perspectives on Latrine Use, Child Feces Disposal, and Clean Play Environments in Western Kenya.
Exposure to fecal pathogens contributes to childhood diarrhea and stunting, causing harmful short- and long-term impacts to health. Understanding pathways of child fecal exposure and nutritional deficiencies is critical to informing interventions to reduce stunting. Our aim was to explore determinants of latrine use, disposal of child feces, and perceptions and provisions of a safe and clean child play environment among families with children under two (CU2) years to inform the design of a behavior change intervention to address water, sanitation, and hygiene (WASH), and nutrition behaviors. In 2016, we conducted a mixed-methods formative research in western Kenya. We conducted 29 key informant interviews with community leaders, health workers, and project staff; 18 focus group discussions with caregivers of CU2 years; and 24 semi-structured household observations of feeding, hygiene, and sanitation behaviors. We used the capability, opportunity, motivation, and behavior model as our theoretical framework to map caregiver behavioral determinants. Latrine use barriers were lack of latrines, affordability of lasting materials, and social acceptability of unobserved open defecation. Barriers to safe disposal of child feces were lack of latrines, time associated with safe disposal practices, beliefs that infant feces were not harmful, and not knowing where children had defecated. Primary barriers of clean play environments were associated with creating and maintaining play spaces, and shared human and animal compounds. The immediate cost to practicing behaviors was perceived as greater than the long-term potential benefits. Intervention design must address these barriers and emphasize facilitators to enable optimal WASH behaviors in this context.


Flower-like droplets obtained by self-emulsification of a phase-separating (SEPS) aqueous film.
Self-emulsification, referring to the spontaneous formation of droplets of one phase in another immiscible phase, is attracting growing interest because of its simplicity in creating droplets. Existing self-emulsification methods usually rely on phase inversion, temperature cycling, and solvent evaporation. However, achieving spatiotemporal control over the morphology of self-emulsified droplets remains challenging. In this work, a conceptually new approach of creating both simple and complex droplets by self-emulsification of a phase-separating (SEPS) aqueous film, is reported. The aqueous film is formed by depositing a surfactant-laden aqueous droplet onto an aqueous surface, and the fragmentation of the film into droplets is triggered by a wetting transition. Smaller and more uniform droplets can be achieved by introducing liquid-liquid phase separation (LLPS). Moreover, properly modulating quadruple LLPS and film fragmentation enables the creation of highly multicellular droplets such as flower-like droplets stabilized by the interfacial self-assembly of nanoparticles. This work provides a novel strategy to design aqueous droplets by LLPS, and it will inspire a wide range of applications such as membraneless organelle synthesis, cell mimics and delivery.


A new measure of orthogonality for multi-dimensional chromatography.
Multi-dimensional chromatographic techniques, such as (comprehensive) two-dimensional liquid chromatography and (comprehensive) two-dimensional gas chromatography, are increasingly popular for the analysis of complex samples, such as protein digests or mineral oils. The reason behind the popularity of these techniques is the superior performance, in terms of peak-production rate (peak capacity per unit time), that multi-dimensional separations offer compared to their one-dimensional counterparts. However, to fully utilize the potential of multi-dimensional chromatography it is essential that the separation mechanisms used in each dimension be independent of each other. In other words, the two separation mechanisms need to be orthogonal. A number of algorithms have been proposed in the literature for measuring chromatographic orthogonality. However, these methods have their limitations, such as reliance on the division of the separation space into bins, need for specialist software or requirement of advanced programming skills. In addition, some of the existing methods for measuring orthogonality include regions of the separation space that do not feature peaks. In this paper we introduce a number of equations which provides information on the spread of the peaks within the separation space in addition to measuring orthogonality, without the need for complex computations or division of the separation space into bins.