Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution.
Hormone replacement therapy (HRT) is commonly prescribed to treat menopausal symptoms and to prevent post-menopausal bone loss. However, many women are concerned about hormonal replacement therapy because they believe that such treatment will result in weight gain. The effect of HRT on weight and body fat distribution has not yet been examined in systematic reviews. It is an important topic since many women decline oestrogen therapy due to their concerns about resultant weight gain, and thus forego its potential therapeutic benefits. To evaluate the effect of unopposed oestrogen or combined oestrogen and progestogen hormone replacement therapy (HRT) upon the weight and body fat distribution of perimenopausal and postmenopausal women. The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of randomised controlled trials (RCTs). Computerised searches of MEDLINE, EMBASE, Current Contents, Biological Abstracts and CINAHL were performed. Attempts were made to identify trials from citation lists of review articles and relevant papers already obtained. In most cases, first authors of each eligible trial were contacted for additional information. All those trials that had been located as at August 1998 were examined for eligibility. All randomised, placebo or no treatment controlled trials that detailed the effect of HRT on weight or body fat distribution, including studies where HRT was combined with other therapy such as diet, supplements or exercise. Studies were eligible for consideration even though the main focus of the trial may have been on another aspect of HRT. Previous HRT use should have ceased at least one month (in the case of patches, cream or gel) or three months (for oral preparations or subcutaneous pellets) before commencement of the study. Twenty two RCTs were identified that fulfilled the inclusion criteria for this review. The results of one trial were not available in a form that allowed it to be included in the meta-analysis; however, it has been included in the text of the review for discussion. Twenty four RCTs are awaiting assessment pending additional information from first authors. Two reviewers extracted the data independently, and the weighted mean differences for continuous outcomes were estimated from the data. Results for unopposed oestrogen and combined oestrogen were analysed separately, and the effect of each treatment regimen on body weight, BMI, waist-hip ratio, fat mass and skinfold measurement was examined where available. The effect of differing dosage levels on these parameters was also examined. Outcomes were evaluated separately for unopposed oestrogen and oestrogen/progestogen regimens. Statistical analysis was performed using the weighted mean difference for continuous outcomes as recommended by the Cochrane Menstrual Disorders and Subfertility Group. No statistically significant difference was found in mean weight gain between those using unopposed oestrogen and non-HRT users (0.66 kg, 95% CI -0.62, 1.93). No significant difference was found in mean weight gain between those using oestrogen/progestogen therapy and non-HRT users (-0.47 kg, 95% CI -1.63, 0.69). Insufficient data exist to enable meta-analysis of the effect of unopposed oestrogen on BMI. The reviewers found no statistically significant difference in mean BMI increase between those using oestrogen/progestogen and non-HRT users (-0.50, 95% CI -1.06, 0.06). Insufficient data exist to enable meta-analysis of the effect of HRT on waist-hip ratio, fat mass or skinfold thickness. There is evidence of no effect of unopposed oestrogen or combined oestrogen on body weight, indicating that these regimens do not cause extra weight gain in addition to that normally gained at menopause. (ABSTRACT TRUNCATED)


SV40 large T-antigen: dual oncogene.
Simian virus 40 (SV40) is a small, DNA-containing tumour virus. One of its gene products, the large tumour antigen (T-ag), is essential for both viral replication and cell transformation. SV40 T-ag can be considered a dual oncogene protein; it is a composite transforming protein that provides distinct functions at different subcellular locations. In addition to its roles in virus replication, T-ag exerts numerous effects on host cells. Those cellular effects reflect viral stimulation of host cell entry into S phase. Numerous chemical modifications have been ascribed to T-ag. They might be involved in defining subpopulations of T-ag that are, in turn, responsible for mediating various T-ag biochemical functions. The T-ag polypeptide, 90,000-100,000 in molecular weight, appears to contain multiple, discrete functional domains; several biological activities have been assigned to relatively small defined regions of the molecule. The cellular progenitors of the T-ag biochemical activities are not obvious. A cellular protein, p53, thought to be involved in regulation of cell proliferation, becomes complexed with T-ag in transformed cells and is stabilized. The interaction of T-ag with this cellular substrate may play an important part in SV40 transformation. T-ag and T-ag/p53 complexes are localized in both the nucleus and plasma membrane of transformed cells. T-ag is transported to the nucleus because of a 7-residue nuclear transport signal contained within its primary sequence. Its migration to the membrane is by an unknown pathway. Only a minor fraction of the total cellular T-ag is present at the cell surface. Both amino and carboxy termini of the T-ag polypeptide are exposed on the extracellular face of the cell. Nuclear and membrane T-ag are structurally very similar, although a portion of membrane T-ag is acylated and nuclear T-ag is not. The nuclear and membrane forms of T-ag apparently provide separate and complementary functions necessary for cell transformation. Nuclear T-ag is important in immortalizing primary cells and membrane T-ag may mediate more pronounced morphological changes. A model is presented, postulating how the two forms of T-ag might cooperate to mediate phenotypic transformation.


Object-carrying by rats: an approach to the behavior produced by brain stimulation.
Rats were provided with opportunity to turn reinforcing hypothalamic stimulation on and off by traversing back and forth across a chamber. When provided with edible and inedible objects, all animals that self-stimulated carried them from the stimulation to the nonstimulation side. Neither food deprivation nor a history of stimulus-bound eating produced a preference for the edible objects. Equivalent stimulation provided without regard to the animals' location in the chamber did not elicit object-carrying. Results are interpreted in terms of the natural conditions which normally elicit this species-specific unit of behavior. Implications for understanding other behavior patterns elicited by hypothalamic stimulation are suggested.


In vivo fate of 125I SS-B (La) injected into mice.
The fate of the radiolabelled soluble cellular antigen SS-B (La) was compared with that of other 125I-labelled proteins of known molecular weight (MW) and electrostatic charge, following i.v. injection into BALB/c mice. The plasma half-life of 125I-SS-B was 3 min, while that of 125I-bovine serum albumin (similar MW and electrostatic charge) was 270 min. 125I-heat-aggregated IgG (MW greater than 1 x 10(6)) and 125I-7S human IgG (MW 168,000) had plasma half-lives of 40 min and greater than 300 min, respectively. Liver and kidney showed preferential uptake of 125I-SS-B, followed by a rapid decrease in radioactivity. During this time low MW, trichloroacetic acid (TCA) soluble, material appeared in urine. This suggests a specific uptake mechanism followed by a catabolic phase. These studies demonstrate that normal mice remove 125I-SS-B rapidly from the circulation and then degrade it. This rapid antigen elimination may protect against the induction of potentially harmful autoantibody responses.


Regulation of CD1d expression and function by a herpesvirus infection.
Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that the lytic replication cycle of the Kaposi sarcoma-associated herpesvirus (KSHV) promotes downregulation of cell-surface CD1d. This is caused by expression of the 2 modulator of immune recognition (MIR) proteins of the virus, each of which promotes the loss of surface CD1d expression following transfection into uninfected cells. Inhibition of CD1d surface expression is due to ubiquitination of the CD1d alpha-chain on a unique lysine residue in its cytoplasmic tail, which triggers endocytosis. Unlike MIR-mediated MHC class I downregulation, however, CD1d downregulation does not appear to include accelerated lysosomal degradation. MIR2-induced downregulation of CD1d results in reduced activation of CD1d-restricted T cells in vitro. KSHV modulation of CD1d expression represents a strategy for viral evasion of innate host immune responses and implicates CD1d-restricted T cells as regulators of this viral infection.


Immediate and early replacement implants and restorations.
There have been rapid developments in dental implant treatment protocols to reduce the time between implant placement and restoration. Implants may be placed immediately following tooth extraction or following a period of healing to allow resolution of residual infection or sufficient bone and soft tissue healing. Early restoration and loading of implants has to be carefully controlled to avoid increased failure and complications. Advantages and disadvantages of the various techniques are described. The clinician should adopt a treatment protocol that ensures a high success rate and a long-term functional and aesthetic implant restoration. Rapid treatment protocols can be considered when they do not compromise these goals, and the clinician is sufficiently experienced in their application.


Warped functional analysis of variance.
This article presents an Analysis of Variance model for functional data that explicitly incorporates phase variability through a time-warping component, allowing for a unified approach to estimation and inference in presence of amplitude and time variability. The focus is on single-random-factor models but the approach can be easily generalized to more complex ANOVA models. The behavior of the estimators is studied by simulation, and an application to the analysis of growth curves of flour beetles is presented. Although the model assumes a smooth latent process behind the observed trajectories, smootheness of the observed data is not required; the method can be applied to irregular time grids, which are common in longitudinal studies.


[Correction of apathetic-abulic manifestations of schizophrenia with cholinotropic drugs].
The authors describe the results of the treatment of 30 patients suffering from schizophrenia with the well-defined apatho-abulic manifestations. The patients received anticholin-esterase agents (galanthamine and deoxypeganin) combined with the M-cholinolytic drug benactyzine. The treatment lasted 3 to 4 weeks. Satisfactory compensation for the deficiency manifestations was attained in 18 patients (60%). The therapeutic dynamics appeared the best in patients with predominant anergic disorders accompanied by well-defined impoverishment of motor functions. The presence of roductive psychotic disorders in the syndromal structure noticeably decreased the treatment efficacy. The deranged capacity for behavioral initiation classified by the authors with the fundamental deficiency manifestations turned out most refractory to the treatment. The polymediator model of the schizophrenic defect is reviewed, according to which the deficiency manifestations represent adaptive stability states with emergence to a lower energy level. In such a case the neuronal populations with different mediator modality become deactivated. On the one hand, this gives rise to a decrease of psychotic productive disorders, on the other one, to the occurrence of the negative manifestations.


Embryonic and postnatal development of GABA, calbindin, calretinin, and parvalbumin in the mouse claustral complex.
We analyzed the development of immunoreactive expression patterns for the neurotransmitter gamma-aminobutyric acid (GABA) and the calcium-binding proteins calbindin, calretinin, and parvalbumin in the embryonic and postnatal mouse claustral complex. Each calcium-binding protein shows a different temporal and spatial pattern of development. Calbindin-positive cells start to be seen very early during embryogenesis and increase dramatically until birth, thus becoming the most abundant cell type during embryonic development, especially in the ventral pallial part of the claustrum. The distribution of calbindin neurons throughout the claustrum during embryonic development partly parallels that of GABA neurons, suggesting that at least part of the calbindin neurons of the claustral complex are GABAergic and originate in the subpallium. Parvalbumin cells, on the other hand, start to be seen only postnatally, and their number then increases while the density of calbindin neurons decreases. Based on calretinin expression in axons, the core/shell compartments of the dorsal claustrum start to be clearly seen at embryonic day 18.5 and may be related to the development of the thalamoclaustral input. Comparison with the expression of Cadherin 8, a marker of the developing dorsolateral claustrum, indicates that the core includes a central part of the dorsolateral claustrum, whereas the shell includes a peripheral area of the dorsolateral claustrum, plus the adjacent ventromedial claustrum. The present data on the spatiotemporal developmental patterns of several subtypes of GABAergic neurons in the claustral complex may help for future studies on temporal lobe epilepsies, which have been related to an alteration of the GABAergic activity.


Endogenous pyrogen activity in human plasma after exercise.
Plasma obtained from human subjects after exercise and injected intraperitoneally into rats elevated rat rectal temperature and depressed plasma iron and zinc concentrations. The pyrogenic component was heat-denaturable and had an apparent molecular weight of 14,000 daltons. Human mononuclear leukocytes obtained after exercise and incubated in vitro released a factor into the medium that also elevated body temperature in rats and reduced trace metal concentrations. These results suggest that endogenous pyrogen, a protein mediator of fever and trace metal metabolism during infection, is released during exercise.


Peripheral Nerve Stimulation for the Management of Pediatric Neuropathic Pain.
The management of neuropathic pain in children poses an enormous challenge for pediatricians and pain management physicians. Current treatment options include physical therapy and medication management. Peripheral nerve stimulation/neuromodulation is a novel and minimally invasive treatment that can be initiated and monitored in an outpatient setting. This new technology can be a useful tool for treating pain secondary to pediatric neuropathy and chronic refractory pain after conservative management. Our case report describes the use of a peripheral nerve stimulator in the successful management of pediatric neuropathic leg pain.


The suggestibility of children's memory.
In this review, we describe a shift that has taken place in the area of developmental suggestibility. Formerly, studies in this area indicated that there were pronounced age-related differences in suggestibility, with preschool children being particularly susceptible to misleading suggestions. The studies on which this conclusion was based were criticized on several grounds (e.g. unrealistic scenarios, truncated age range). Newer studies that have addressed these criticisms, however, have largely confirmed the earlier conclusions. These studies indicate that preschool children are disproportionately vulnerable to a variety of suggestive influences. There do not appear to any strict boundary conditions to this conclusion, and preschool children will sometimes succumb to suggestions about bodily touching, emotional events, and participatory events. The evidence for this assertion is presented in this review.


[Combined general anesthesia and high thoracic epidural analgesia in myocardial revascularization of the failing heart in a patient on hemodialysis].
Terminal renal failure is often associated with severe coronary artery disease that should be treated with surgical myocardial revascularization. Since perioperative morbidity and mortality rates in these patients are high, the best way and the time for surgical intervention are still uncertain. We present the patient with end-stage renal disease, on chronic program of hemodialysis, who had underwent off-pump coronary artery bypass grafting and high thoracic epidural anaesthesia, followed by early extubation. To our knowledge, off-pump surgical myocardial revascularization in patients on hemodialysis using this anaesthetic technique has not yet been presented in our literature.


Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats: Correlation to Behavioural Activity State, Effect of Handling and Tail-Pinch.
Hippocampal extracellular levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were monitored with the microdialysis technique in freely moving rats. In one experiment 30 min samples were collected during 24 h of continuous perfusion, and the monoamine output was compared to the behavioural activity state, as arbitrarily classified in three categories: sleep/rest, drowsiness and full alertness associated with complex behaviours. In the individual animal the hippocampal NA and 5-HT output showed pronounced fluctuations during the 24 h period, but the 30 min sampling times did not allow for a clear-cut correlation to behavioural activity state. However, the mean NA and 5-HT output for all animals during the dark period of the day was 43 and 38% higher, respectively, than during the light period, and the average NA and 5-HT levels in samples collected during periods of high behavioural activity was 34 and 45% higher, respectively, than during periods of rest or sleep. In contrast, there were no detectable changes in extracellular 5-HIAA. The selective serotonin uptake blocker indalpine, added to the perfusion fluid at 1 microM, increased the extracellular 5-HT levels 6-fold, with a similar correlation to behavioural activity state as without indalpine. In a second experiment the effect of handling and tail-pinch was studied in 15 min sample fractions. Gentle handling of the animals during the sampling period increased the hippocampal NA and 5-HT output by 32 and 72%, respectively, and a similar increase (63 and 48%) was obtained by application of tail-pinch. Maximum NA output was reached during the handling or tail-pinch period, whereas maximal 5-HT levels were detected in the subsequent 15 min sample fraction. No changes in extracellular 5-HIAA was observed. It is concluded (1) that intracerebral microdialysis provides a useful method for the study of extracellular NA and 5-HT in the hippocampal formation of conscious rats during active behaviour; (2) that there are substantial fluctuations in hippocampal NA and 5-HT output in freely moving rats which correlate with the light - dark cycle as well as with the activity state of the animals; (3) that the spontaneous variations in 5-HT output are maintained during reuptake blockade; and (4) that behavioural activation through gentle handling or tail-pinch elicits NA and 5-HT release. The present data support a role of the forebrain NA and 5-HT systems in behavioural state control and highlights the necessity of experimental designs in which the spontaneous fluctuations in transmitter release are controlled for in studies of, for example, drug effects on NA and 5-HT release in conscious animals.


Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism.
Prolonged excessive consumption of alcohol has been associated with a variety of cognitive disorders accompanied by neuropathological and neurochemical abnormalities of the brain, particularly in the frontal lobes. Studies with positron emission tomography (PET) have shown decreased local cerebral metabolic rates for glucose (lCMRglc) in frontal regions, with correlated abnormalities on neuropsychological tests sensitive to executive functioning. This investigation was designed as a pilot study to examine the effects of abstinence and relapse in patients with severe chronic alcoholism studied longitudinally with PET and with neuropsychological evaluation to assess both general and executive functioning. Six patients, including 4 who remained relatively abstinent and 2 who relapsed following their initial evaluation, were studied twice, with inter-evaluation intervals ranging from 10 to 32 months. The patients who remained abstinent or who had minimal alcohol use showed partial recovery of lCMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. These results, although based upon a relatively small number of subjects, provide preliminary support for at least partial recovery of metabolic and cognitive functioning in individual patients who abstain from alcohol.


Photodynamic therapy for multiple central type lung cancer - a case report.
In case of central type lung cancer, it happens that tumors tend to grow at many foci of bronchial tree, sometimes simultaneously and sometimes not. And these patients with such abnormalities often suffer from pulmonary emphysema or chronic bronchitis because of heavy smoking habits. So it is important to choose the treatment which preserve the pulmonary function in these cases. Today among several kinds of treatments, photodynamic therapy (PDT) is the definite method to maintain lung function. We report here a case of multiple central type lung cancer treated successfully by PDT.


The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.
Age-related obesity significantly increases the risk of chronic diseases such as type 2 diabetes, cardiovascular diseases, hypertension, and certain cancers. The insulin-leptin axis is crucial in understanding metabolic disturbances associated with age-related obesity. Rho GTPase Cdc42 is a member of the Rho family of GTPases that participates in many cellular processes including, but not limited to, regulation of actin cytoskeleton, vesicle trafficking, cell polarity, morphology, proliferation, motility, and migration. Cdc42 functions as an integral part of regulating insulin secretion and aging. Some novel roles for Cdc42 have also been recently identified in maintaining glucose metabolism, where Cdc42 is involved in controlling blood glucose levels in metabolically active tissues, including skeletal muscle, adipose tissue, pancreas, etc., which puts this protein in line with other critical regulators of glucose metabolism. Importantly, Cdc42 plays a vital role in cellular processes associated with the insulin and leptin signaling pathways, which are integral elements involved in obesity development if misregulated. Additionally, a change in Cdc42 activity may affect senescence, thus contributing to disorders associated with aging. This review explores the complex relationships among age-associated obesity, the insulin-leptin axis, and the Cdc42 signaling pathway. This article sheds light on the vast molecular web that supports metabolic dysregulation in aging people. In addition, it also discusses the potential therapeutic implications of the Cdc42 pathway to mitigate obesity since some new data suggest that inhibition of Cdc42 using antidiabetic drugs or antioxidants may promote weight loss in overweight or obese patients.


Evaluation of endometrial biopsy using an aspiration curet without cervical tenaculum.
In a study of 132 women having endometrial biopsy with either a Novak or Randall aspiration curet before hysterectomy, a tenaculum was not used initially if the curet could be passed easily through the cervix. One biopsy specimen was taken from the anterior endometrium and one from the posterior endometrium. Biopsy was successful in 80 women (61%) and unsuccessful in 52 (39%). Women who are premenopausal, who do not have cervical stenosis, and who have a uterus that sounds to 3.5 inches or less are significantly more likely to have a successful biopsy. Excluding six women in whom the curet could not be passed through the cervix, adequate tissue for histologic evaluation was obtained in 101 of 126 women (80%). Furthermore, endometrial biopsy accurately reflected histopathologic features of the surgical specimen in 98% (98/101) of the women who had sufficient tissue obtained for evaluation. Endometrial biopsy done with an aspiration curet but without placing a tenaculum on the cervix should be attempted in women who require evaluation. Endometrial biopsy would appear to rival dilation and curettage for obtaining endometrial tissue that accurately reflects endometrial histopathology.


Multispectral Imaging for Vein Localization and Contrast Enhancement.
Intravenous (IV) catheterization is a common procedure. Still, there is a 26% chance of the first attempt catheterization failure due to the changing visibility of veins because of the patient's skin tone and body fat content. Ultrasound assistive devices help locate deeper veins but are not practical in emergencies, and transillumination assistive devices have a low field of view. Commercial near-infrared (NIR) imaging devices are effective in vein localization but are expensive and are not used in low-cost clinical settings. To overcome this, NIR Multispectral Imaging (MSI) was used to find the optimal wavelength that provides the enhanced visualization of veins for all skin types and Body Mass Index (BMI). The band with the highest vein-to-skin contrast ratio was selected and contrast enhancement was done using our proposed method. The primary blocks of the proposed method are Gamma correction, Contrast Limited Adaptive Histogram Equalization (CLAHE), Adaptive Thresholding, and image Fusion. The optimal spectral range was found to be 814-876 nm and our method increased the contrast by 0.41, 0.375, and 0.39 for fair, brown, and dark brown skin types, respectively, with different BMI.Clinical relevance- From the study, we can develop a potentially low-cost vein localization assistive device for training medical and nursing students and use it in emergencies for venous access to improve confidence in IV catheterization.


Benefit of Qigong exercise in patients with fibromyalgia: a pilot study.
Fibromyalgia (FM) patients present with widespread chronic pain and other symptoms. Some studies in the literature have reported inconsistent results after a Qigong exercise intervention in patients with FM. The purpose of this study was to test the feasibility of a home-based Qigong exercise in patients with FM. A total of 14 subjects were randomly assigned into one of two groups. The experimental group went through a six-week Qigong exercise program involving meditation, deep breathing, and synchronized rhythmic body movements. The control group took part in a sham Qigong exercise program using the same body movements also for six weeks. Clinical assessments at baseline and end of intervention used the Short-Form McGill Pain Questionnaire, Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, and Fibromyalgia Impact Questionnaire. Group mean scores of four measurements were significantly (p < .0125) reduced in the intervention group, but not in the control group. The percentage changes in the four measurements were 44.2%, 24.8%, 37.3%, and 44.3% in the intervention group, and 10.1%, 6.3%, 9.9%, and 11.8% in the control group. Qigong exercise may potentially be an effective self-management approach in controlling FM symptoms. In this pilot study, regular daily Qigong exercise, accumulated number of exercise sessions, and the specific form of Qigong exercise may all be important factors for the significant improvement in the study subjects. Future research is required to determine whether the same benefit can be obtained in a larger sample.


Motor unit number in a small facial muscle, dilator naris.
A loss of functioning motor units underlies many neuromuscular disorders. The facial nerve innervates the muscles of facial expression, including nasal muscles, which also play an important role in the regulation of airflow resistance. It is difficult to accurately assess motor unit number in the facial muscles, because the muscles are difficult to activate in isolation. Here, we apply the manual McComas method to estimate the number of motor units in a nasal dilator muscle. EMG of the dilator naris was recorded during graded stimulation of the zygomatic branch of the facial nerve in 26 subjects (12 males and 14 females), aged 20-41 years. Each subject was studied twice, on separate days, to estimate method reproducibility. As a check on our use of the McComas method, we also estimated motor unit number in the first dorsal interosseus muscle (FDI) of six subjects, as the muscle is also small and has been studied with the McComas method. Reproducibility was evaluated with a rigorous statistical approach, the Bland-Altman procedure. We estimate that dilator naris is composed of 75 ± 15.6 (SD) motor units, compared to 144 ± 35.5 in FDI. The coefficient of variation for test-retest reproducibility of dilator naris motor unit estimates was 29.6 %, similar to separate-day reproducibility reported for other muscles. Recording and stimulation were done with surface electrodes, and the recordings were of high quality and reproducible. This simple technique could be applied clinically to track motor neuron loss and to monitor facial nerve integrity.


Dimensionally and compositionally controlled growth of calcium phosphate nanowires for bone tissue regeneration.
Nanostructured biomaterials with controlled morphology and composition are of high interest for bone tissue regeneration. As resorbable and biocompatible materials for bone tissue engineering, calcium phosphate nanowires and nanoneedles with different aspect ratios and compositions have been first synthesized without the use of any toxic surfactants via an energy efficient microwave assisted process. Correlation between solvent composition, mixing methodology and reagent stoichiometric ratios was investigated with the aim of producing orientated growth and varied biphasic composition, resulting in dimensionally controlled growth of materials containing varying hydroxyapatite (HA)/monetite quantities. It was observed that the HA/monetite content and dimensionality could be manipulated by changing the initial ethanol (EtOH) volume in the H2O/EtOH solvent mixture. Three dimensional particles with minute amounts of HA were produced when a H2O/EtOH volumetric ratio of 20/80 was used. Conversely, high aspect ratio (ca. 54) nanowires containing ca. 38 wt% HA were obtained with a 60/40 H2O/EtOH volumetric ratio. Importantly, the quantity of HA in the high aspect ratio nanowires/needles was controlled by varying the stoichiometric ratio of the reactants, demonstrating that one-dimensional materials with close to 100% HA can be achieved when the Ca/P ratio is increased to 1.67. Additionally, significant correlation between the extent of orientated growth of the materials and the point of EtOH addition during the mixing method was observed. The findings highlight that solvent composition, reactant stoichiometric ratio and mixing procedure can be used in tandem to tailor the morphology and composition of calcium phosphate materials, which are of very high importance in developing excellent materials suitable for bone tissue regeneration.


Pre-registration diploma student nurse stress and coping measures.
The aim of this study is to examine the stress experiences and coping abilities of student nurses. A survey design was employed to examine the stress experiences of Diploma student nurses in a large Dublin Teaching Hospital. A questionnaire was utilized that measured and explored five specific constructs pertinent to student nurse stress. These included clinical stress, academic stress, coping, emotions and personal factors which assist students nurses during periods of stress. Findings showed that examinations, the level and intensity of academic workload, the theory-practice gap and poor relationships with clinical staff were the leading stressors identified. Emotional reactions to stress included feeling exhausted and upset under pressure. Students adopted short-term emotion focused coping strategies when attempting to deal with stress. A sense of achievement, and determination, were personal factors, which assisted students to continue in the event of stress being present. Content analysis of the open questions shed further light in relation to the stress phenomenon, particularly in relation to clinical stress. The provision of adequate support services from a clinical and academic perspective, a lecture-practitioner model of education delivery, and curriculum changes which focus on developing student self awareness skills are the suggested study recommendations.


Cytidine-to-Uridine RNA Editing Factor NbMORF8 Negatively Regulates Plant Immunity to Phytophthora Pathogens.
Mitochondria and chloroplasts play key roles in plant-pathogen interactions. Cytidine-to-uridine (C-to-U) RNA editing is a critical posttranscriptional modification in mitochondria and chloroplasts that is specific to flowering plants. Multiple organellar RNA-editing factors (MORFs) form a protein family that participates in C-to-U RNA editing, but little is known regarding their immune functions. Here, we report the identification of NbMORF8, a negative regulator of plant immunity to Phytophthora pathogens. Using virus-induced gene silencing and transient expression in Nicotiana benthamiana, we show that NbMORF8 functions through the regulation of reactive oxygen species production, salicylic acid signaling, and accumulation of multiple Arg-X-Leu-Arg effectors of Phytophthora pathogens. NbMORF8 is localized to mitochondria and chloroplasts, and its immune function requires mitochondrial targeting. The conserved MORF box domain is not required for its immune function. Furthermore, we show that the preferentially mitochondrion-localized NbMORF proteins negatively regulate plant resistance against Phytophthora, whereas the preferentially chloroplast-localized ones are positive immune regulators. Our study reveals that the C-to-U RNA-editing factor NbMORF8 negatively regulates plant immunity to the oomycete pathogen Phytophthora and that mitochondrion- and chloroplast-localized NbMORF family members exert opposing effects on immune regulation.


Cystic Fibrosis Transmembrane Conductance Regulator-Related Metabolic Syndrome and Cystic Fibrosis Screen Positive, Inconclusive Diagnosis.
An unintended consequence of cystic fibrosis (CF) newborn screening (NBS) is the identification of infants with a positive NBS test but inconclusive diagnostic testing. These infants are classified as CF transmembrane conductance regulator-related metabolic syndrome (CRMS) in the US and CF screen positive, inconclusive diagnosis (CFSPID) in other countries. Diagnostic and management decisions of these infants are challenges for CF healthcare professionals and stressful situations for families. As CF NBS has become more widespread across the world, increased information about the epidemiology and outcomes of these infants is becoming available. These data were reviewed at the 2015 CF Foundation Diagnosis Consensus Conference, and a harmonized definition of CRMS and CFSPID was developed. At the consensus conference, participants reviewed published and unpublished studies of CRMS/CFSPID and used a modified Delphi methodology to develop a harmonized approach to the definition of CRMS/CFSPID. Several studies of CRMS/CFSPID from populations around the world have been published in the past year. Although the studies vary in the number of infants studied, study design, and outcome measures, there have been some consistent findings. CRMS/CFSPID occurs relatively frequently, with CF:CRMS that ranges from 3 to 5 cases of CF for every 1 case of CRMS/CFSPID in regions where gene sequencing is not used. The incidence varies by NBS protocol used, and in some regions more cases of CRMS/CFSPID are detected than cases of CF. The majority of individuals with CRMS/CFSPID do not develop CF disease or progress to a diagnosis of CF. However, between 10% and 20% of asymptomatic infants can develop clinical features concerning for CF, such as a respiratory culture positive for Pseudomonas aeruginosa. Most studies have only reported short-term outcomes in the first 1-3 years of life; the long-term outcomes of CRMS/CFSPID remain unknown. The European CF Society definition of CFSPID and the CF Foundation definition of CRMS differ only slightly, and the consensus conference was able to create a unified definition of CRMS/CFSPID. CRMS/CFSPID is a relatively common outcome of CF NBS, and clinicians need to be prepared to counsel families whose NBS test falls into this classification. The vast majority of infants with CRMS/CFSPID will remain free from disease manifestations early in life. However, a small proportion may develop clinical features concerning for CF or demonstrate progression to a clinical phenotype compatible with a CF diagnosis, and their long-term outcomes are not known. A consistent international definition of CRMS/CFSPID will allow for better data collection for study of outcomes and result in improved patient care.


Natural course of progression of liver fibrosis in Japanese patients with chronic liver disease type C--a study of 527 patients at one establishment.
Patients with chronic hepatitis C infection show a gradual progression of fibrosis to liver cirrhosis and hepatocellular carcinoma (HCC). We studied whether the progression of liver fibrosis differed among Japanese subjects who were infected with different hepatitis C virus (HCV) genotypes. In 527 patients we examined whether there was a relationship between gender, age, history of blood transfusion, interval between date of blood transfusion and date of liver biopsy or date of diagnosis of HCC, serum alanine aminotransferase level, platelet count or HCV genotype, with the extent of liver fibrosis, classified into four stages (F1-F4). Moreover, we compared the mean rate of liver fibrosis progression per year in patients with each HCV genotype. Patients who had a higher fibrosis score tended to be older, have a lower platelet count and a longer interval since blood transfusion than those who had a lower fibrosis score. The mean rate of liver fibrosis progression was 0.12 +/- 0.15 stages per year after the blood transfusion. However, the progression rate of liver fibrosis in patients who had received a blood transfusion when they were > or = 30 years of age was 0.19 +/- 0.22, while the progression rate of liver fibrosis in the patients who had received a blood transfusion when they were < 30 years was 0.09 +/- 0.09. In conclusion, chronic hepatitis C is a progressive disease, and patients with genotype 1b, 2a and 2b have a similar rate of progression of liver fibrosis. Particular attention should be paid to patients who are infected with HCV when > or = 30 years of age, because intrahepatic fibrosis rapidly progresses in these patients.


[Transient hyperphosphatasemia in infants and young children].
Transient hyperphosphatasemia of infancy. Striking transient increases in serum alkaline phosphatase in nine new cases are reported. The etiology is still unknown. The patients were 6.5 months to 30 months of age and none showed any clinical evidence of hepatic or skeletal disease. Values became normal within 12 weeks in all patients. It is important to know this condition to avoid unnecessary and expensive diagnostic procedures. Though hyperphosphatasemia does not seem to give any problems we recommend a brief diagnostic protocol in order to recognize transient hyperphosphatasemia of infancy.


Inadvertent hypothermia in paediatric radiotherapy practices under sedation: a single centre observational study.
To detect changes in body temperature during outpatient procedures and to identify factors associated with hypothermia in the paediatric population undergoing radiotherapy under sedation. The observational study was conducted between July and October 2022 at Ankara City Hospital, Turkey, and comprised paediatric cancer patients aged from 1 month to 18 years who needed sedation or general anaesthesia during radiotherapy. Baseline body temperature T1 was measured before transportation to the radiotherapy room, while body temperature T2 was taken after radiotherapy. Data was analysed using SPSS 20. A total of 152 radiotherapy sessions related to 13 children were evaluated. There were 8(61%) boys and 5(38%) girls with overall mean 4.46±3.45 years (range: 2-13 years). The mean body surface area as 0.70±0.212. Radiotherapy was performed in 9(69%) patients, while 4(31%) patients underwent tomotheraphy. The dose used was 180cGy in 12(92.3%) patients. Hypothermia was observed in at least one session in 12(92.3%) patients. There was significant difference in body temperature at baseline and post-radiotherapy (p<0.05). There were significant changes in body temperature during outpatient procedures in the paediatric population undergoing radiotherapy under sedation.


Central thromboxane receptors: mRNA expression and mediation of pressor responses.
These studies tested whether activation of central thromboxane (Tx)A2/prostaglandin (PG) H2 receptors raises blood pressure (BP). Messenger RNA for TxA2/PGH2 receptors was detected in normal Sprague-Dawley rat brain and in rat neuronal and astroglial brain cells in culture. The mean arterial blood pressure (MAP) was recorded in conscious rats during graded administration of the TxA2/PGH2 receptor agonist U-46,619 given intracerebroventricularly or intravenously. Because the pressor responses to intracerebroventricular (but not intravenous) U-46,619 were significantly greater in-high-salt compared with low-salt rats, high-salt rats were used for subsequent studies. The rise in MAP with intracerebroventricular administration of U-46,619 was greater than with intravenous administration and was more sustained. A comparison of plasma radioactivity after intracerebroventricular or intravenous injection of [3H]U-46,619 demonstrated that approximately 35% of the drug reached the systemic circulation by 5-15 min after intracerebroventricular administration. Coadministration of a TxA2/PGH2 antagonist, ifetroban, by intravenous or intracerebroventricular routes blocked the pressor responses induced by U-46,619. The half-maximal inhibition for blockade of responses was substantially lower for intracerebroventricular than for intravenous responses (intracerebroventricular: 0.03 +/- 0.01 vs. intravenous: 3.1 +/- 0.6 micrograms/kg; P < 0.001). The intravenous administration of ifetroban (10 micrograms/kg) caused a greater (P < 0.02) inhibition of pressor responses to U-46,619 (1 microgram/kg) given intravenously (81 +/- 3%) compared with U-46,619 given intracerebroventricularly (40 +/- 13%). In conclusion, TxA2/PGH2 receptor mRNA is expressed in neurons, glial, and brain stem of normal rats. The central administration of a TxA2/PGH2 mimetic raises blood pressure by interaction with specific central and peripheral receptors. This response is augmented in rats fed a high-salt compared with a low-salt diet.


Unlinked Mendelian inheritance of red and black pigmentation in snakes: Implications for Batesian mimicry.
Identifying the genetic basis of mimetic signals is critical to understanding both the origin and dynamics of mimicry over time. For species not amenable to large laboratory breeding studies, widespread color polymorphism across natural populations offers a powerful way to assess the relative likelihood of different genetic systems given observed phenotypic frequencies. We classified color phenotype for 2175 ground snakes (Sonora semiannulata) across the continental United States to analyze morph ratios and test among competing hypotheses about the genetic architecture underlying red and black coloration in coral snake mimics. We found strong support for a two-locus model under simple Mendelian inheritance, with red and black pigmentation being controlled by separate loci. We found no evidence of either linkage disequilibrium between loci or sex linkage. In contrast to Batesian mimicry systems such as butterflies in which all color signal components are linked into a single "supergene," our results suggest that the mimetic signal in colubrid snakes can be disrupted through simple recombination and that color evolution is likely to involve discrete gains and losses of each signal component. Both outcomes are likely to contribute to the exponential increase in rates of color evolution seen in snake mimicry systems over insect systems.


Pediatric supracondylar humerus fractures: is surgeon experience a surrogate for the need of open reduction?
Although there are many factors that are likely to influence the need for open reduction and percutaneous pinning (ORPF) in the treatment of pediatric supracondylar humerus fractures (SCHFs), the role of surgeon's experience (as represented by the total number of surgically treated SCHFs) on the need for ORPF has seldom been investigated. We reviewed the data on all completely displaced, pediatric SCHFs that were treated surgically by a single, fellowship-trained, pediatric orthopedic surgeon over the first 10 years of the surgeon's clinical practice. The incidence of ORPF was calculated as the percentage of open reductions among surgically treated, completely displaced, consecutive SCHFs at any given time during the 10-year period. From September 2005 to August 2015, a total of 212 completely displaced SCHFs were treated surgically at our institution by a single surgeon. When analyzing the incidence of ORPFs among surgically treated, completely displaced SCHFs at any given time, a bimodal curve was found: there was an increasing slope over the first 30 surgically treated SCHFs, with a progressive decreasing slope afterward. The incidence of ORPF within the first 10, 20, and 30 surgically treated, completely displaced SCHFs was 10.0, 30.0, and 26.7%, respectively, decreasing to 16.0, 9.0, 6.7, and 5.0% within the first 50, 100, 150, and 200 surgeries, respectively. The incidence of ORPF was almost 17-fold higher within the first 30 surgically treated, completely displaced SCHFs (17%), when compared with the following 182 (1.1%) cases (P<0.00001). Although it is likely that many factors influence the need for ORPF in the treatment of completely displaced SCHFs, surgeon's experience appears to play a significant role. Strategies aimed to accelerate the learning curve in the treatment of pediatric SCHFs should be undertaken.


Sulfatase 1 is an inhibitor of ductal morphogenesis with sexually dimorphic expression in the urogenital sinus.
The prostate gland develops from the urogenital sinus in response to circulating androgens. Androgens initiate and stimulate branching morphogenesis in the urogenital sinus via unknown mediators. Heparan sulfate proteoglycans are important extracellular molecules that sequester many growth factors in the extracellular matrix and facilitate signaling by some growth factors as part of ternary complexes that include growth factors, receptors, and heparan sulfate chains. Several enzymes modify the chemical structure of heparan sulfate to further regulate its activity. An examination of these enzymes for sexually dimorphic expression in the urogenital sinus identified Sulfatase 1 (Sulf1) as an enzyme that was down-regulated in the male urogenital sinus coincident with the initiation of prostatic morphogenesis. Down-regulation of Sulf1 was accompanied by an increase in the most highly sulfated forms of heparan sulfate, and a similar increase was observed in female urogenital sinuses treated with testosterone. Inhibiting de novo sulfation of heparan sulfate blocked prostatic morphogenesis, supporting the importance of heparan sulfate modification for prostate development. To functionally test the specific role of Sulf1 during prostate development, Sulf1 was ectopically expressed in the urogenital sinus. It partially inhibited testosterone-stimulated ductal morphogenesis, and it reduced the activation of fibroblast growth factor receptors as well as the ERK1 and ERK2 MAPKs. These data identify sulfatase 1 as an inhibitor of prostatic branching morphogenesis and growth factor signaling that is down-regulated as part of the normal response to androgen action in the male urogenital sinus.


Implementing an online pharmaceutical service using design science research.
The rising prevalence of chronic diseases is pressing health systems to introduce reforms. Primary healthcare and multidisciplinary models have been suggested as approaches to deal with this challenge, with new roles for nurses and pharmacists being advocated. More recently, implementing healthcare based on information systems and technologies (e.g. eHealth) has been proposed as a way to improve health services. However, implementing online pharmaceutical services, including their adoption by pharmacists and patients, is still an open research question. In this paper we present ePharmacare, a new online pharmaceutical service implemented using Design Science Research. The Design Science Research Methodology (DSRM) was chosen to implement this online service for chronic diseases management. In the paper, DSRM's different activities are explained, from the definition of the problem to the evaluation of the artifact. During the design and development activities, surveys, observations, focus groups, and eye-tracking glasses were used to validate pharmacists' and patients' requirements. During the demonstration and evaluation activities the new service was used with real-world pharmacists and patients. The results show the contribution of DSRM in the implementation of online services for pharmacies. We found that pharmacists spend only 50% of their time interacting with patients, uncovering a clear opportunity to implement online pharmaceutical care services. On the other hand, patients that regularly visit the same pharmacy recognize the value in patient follow-up demanding to use channels such as the Internet for their pharmacy interactions. Limitations were identified regarding the high workload of pharmacists, but particularly their lack of know-how and experience in dealing with information systems (IST) for the provision of pharmaceutical services. This paper summarizes a research project in which an online pharmaceutical service was proposed, designed, developed, demonstrated and evaluated using DSRM. The main barriers for pharmacists' adoption of online pharmaceutical services provision were the lack of time, time management and information systems usage skills, as well as a precise role definition within pharmacies. These problems can be addressed with proper training and services reorganization, two proposals to be investigated in future works.


Feasibility of Using H3PO4/H2O2 in the Synthesis of Antimicrobial TiO2 Nanoporous Surfaces.
Ti6Al4V alloys are the primary materials used for clinical bone regeneration and restoration; however, they are substantially susceptible to biomaterial-related infections. Therefore, in the present work, we applied a controllable and stable oxidative nanopatterning strategy by applying H3PO4, a weaker dissociating acid, as a substitute for H2SO4 in the classical piranha reaction. The results suggest that our method acted as a concomitant platform to develop reproducible diameter-controlled TiO2 nanopores (NPs). Interestingly, our procedure illustrated stable temperature reactions without exothermic responses since the addition of mixture preparation to the nanopatterning reactions. The reactions were carried out for 30 min (NP14), 1 h (NP7), and 2 h (NP36), suggesting the formation of a thin nanopore layer as observed by Raman spectroscopy. Moreover, the antimicrobial activity revealed that NP7 could disrupt active microbial colonization for 2 h and 6 h. The phenotype configuration strikingly showed that NP7 does not alter the cell morphology, thus proposing a disruptive adhesion pathway instead of cellular lysis. Furthermore, preliminary assays suggested an early promoted osteoblasts viability in comparison to the control material. Our work opens a new path for the rationale design of nanobiomaterials with "intelligent surfaces" capable of decreasing microbial adhesion, increasing osteoblast viability, and being scalable for industrial transfer.


Hydrodynamic control of the interface between two liquids flowing through a horizontal or vertical microchannel.
We derive a Fourier expansion for estimating laminar hydrodynamic spreading when two immiscible liquids flow steadily, side by side, at low Reynolds number, in a horizontal microchannel of rectangular cross-section. When the aspect ratio of the height of the channel to its width is small this expansion can be truncated after a couple of terms and solved to yield the steady-state position of the boundary in terms of the constant volumetric flow rates, the aspect ratio and the viscosities of the two liquids. Our formula shows that we can control the location of the liquid boundary at the outlet of the microchannel by adjusting the relative volumetric flow rates of the two inlet streams. If the microchannel is oriented vertically and the volumetric flow rates are very low, the position of the boundary is also influenced by gravitational forces that depend on the relative densities of the two liquids. We have tested solutions to our analytical expansions by running computational fluid dynamics simulations and have found excellent agreement. When the aspect ratio is 0.01 the leading term in the Fourier expansion for the spreading has an accuracy of about 1%. This accuracy deteriorates to about 12% when the aspect ratio is 0.1. An understanding of these spreading mechanisms is fundamental to the design of T-sensors and related microfluidic devices.


Functional mutation of DNA polymerase beta found in human gastric cancer--inability of the base excision repair in vitro.
DNA polymerase beta (polbeta) is one of mammalian DNA polymerases and is known to be involved in a G:T/G:U mismatch repair. In order to investigate an involvement of this enzyme in a base excision repair, we searched a mutation of human polbeta in human gastric cancer and studied a function of the mutation. We observed cancer-specific missense mutations in 6 of 20 samples. All of these mutations were, however, heterozygous. We further analyzed the base excision repair activity of these mutants to know whether these mutants cause an error of mismatch repair. One of these mutants, which resulted in an amino acid substitution of Glu for Lys at codon 295, showed an inhibitory effect by in vitro base excision repair assay, suggesting that this mutation might play some role in carcinogenesis of the gastric mucosa.


The influence of sham feedback on physiological processing during fear-driven stimulation.
Biofeedback constitutes a well-established, non-invasive method to voluntary interfere in emotional processing by means of cognitive strategies. However, treatment durations exhibit strong inter-individual variations and first successes can often be achieved only after a large number of sessions. Sham feedback constitutes a rather untapped approach by providing feedback that does not correspond to the participant's actual state. The current study aims to gain insights into mechanisms of sham feedback processing in order to support new techniques in biofeedback therapy. We carried out two experiments and applied different types of sham feedback on skin conductance responses and pupil size changes during affective processing. Results indicate that standardized but context-sensitive sham signals based on skin conductance responses exert a stronger influence on emotional regulation compared to individual sham feedback from ongoing pupil dynamics. Also, sham feedback should forego unnatural signal behavior to avoid irritation and skepticism among participants. Altogether, a reasonable combination of stimulus features and sham feedback characteristics enables to considerably reduce the actual bodily responsiveness already within a single session.


Food shopping practices are associated with dietary quality in low-income households.
ABSTRACT Nutrition education for low-income audiences often focuses on building skills in food shopping and food resource management to help families receive the best nutrition from the resources they have available. However, empirical evidence for the effect of food shopping practice on dietary quality has been limited. This article presents new analyses from two studies that found an association between food shopping practices and diet quality. Logistic regression of data from 957 respondents from the 1996 National Food Stamp Program Survey found that food shopping practices were significantly (p </= .05) associated with the availability of nutrients in the food the households used during a week. Similarly, analysis of baseline data from 5159 women from selected counties of states who participated in the Expanded Food and Nutrition Education Program found that food shopping practices were significantly (p </= .05) associated with increased consumption of nutrients as measured through a single 24-hour recall. These findings suggest that food shopping practices are an important area for nutrition education with low-income audiences.


The use of enzyme linked immunosorbent assay (ELISA) and direct fluorescent antibody (DFA) methods for diagnosis of Giardia intestinalis.
The aim of this study was to evaluate the value of the direct fluorescent antibody (DFA) techniques reported to have high sensitivity and specificity and the enzyme linked immunosorbent assay (ELISA) test used to determine antigens in stool samples in the routine diagnosis of Giardia intestinalis. When 44 stool samples in which G. intestinalis cysts and/or trophozoites had been seen during native Lugol examination were investigated, positivity detected with the trichrome staining method, monoclonal ELISA method and monoclonal DFA method was found to be 37 (84.0%), 39 (88.6%) and 35 (79.5%) respectively. DFA detected Crytosporidium parvum cysts in addition to G. intestinalis in one sample. Twenty-seven (61.4%) of the samples were positive with all three methods. When compared with the DFA method, the ELISA method had a sensitivity of 88.6%, a specificity of 88.8%, a positive predictive value of 79.5% and a negative predictive value of 20.0% while the trichrome staining method had a sensitivity of 85.7%, a specificity of 77.8%, a positive predictive value of 81.1% and a negative predictive value of 22.2%. There was no statistically significant difference between the DFA and ELISA tests and between the DFA test and the trichrome staining method for diagnosing G. intestinalis (p > 0.05).


Personality and defenses: a cross-cultural study of psychiatric patients and healthy individuals in Nicaragua and Sweden.
This study examined cross-cultural variability in personality and defenses among Nicaraguan and Swedish healthy individuals, patients with borderline personality disorder and schizophrenic disorders by means of the projective perceptual Defense Mechanism Test. The over-all aim was to test the hypothesis proposed by Anthony Marsella of 'severity related cross-cultural variability' suggesting that differences in symptom profile or personality patterns between cultures are most pronounced among healthy individuals and less so among individuals with severe mental disorders as they are perceived as more universal and less culturally determined. The over-all results showed that cross-cultural differences were in accordance with the proposed hypothesis. In addition, there were significant intracultural differences between the different diagnostic groups in both countries. The conclusion is that the Defense Mechanism Test and Partial Least Squares analysis seem to be powerful methods for personality assessment and potentially for cross-cultural research, and culture-specific norms in the Defense Mechanism Test must be employed.


A Distinct Hibiscus sabdariffa Extract Prevents Iron Neurotoxicity, a Driver of Multiple Sclerosis Pathology.
Iron deposition in the brain begins early in multiple sclerosis (MS) and continues unabated. Ferrous iron is toxic to neurons, yet the therapies used in MS do not counter iron neurotoxicity. Extracts of Hibiscus sabdariffa (HS) are used in many cultures for medicinal purposes. We collected a distinct HS extract and found that it abolished the killing of neurons by iron in culture; medications used in MS were ineffective when similarly tested. Neuroprotection by HS was not due to iron chelation or anthocyanin content. In free radical scavenging assays, HS was equipotent to alpha lipoic acid, an anti-oxidant being tested in MS. However, alpha lipoic acid was only modestly protective against iron-mediated killing. Moreover, a subfraction of HS without radical scavenging activity negated iron toxicity, whereas a commercial hibiscus preparation with anti-oxidant activity could not. The idea that HS might have altered properties within neurons to confer neuroprotection is supported by its amelioration of toxicity caused by other toxins: beta-amyloid, rotenone and staurosporine. Finally, in a mouse model of MS, HS reduced disability scores and ameliorated the loss of axons in the spinal cord. HS holds therapeutic potential to counter iron neurotoxicity, an unmet need that drives the progression of disability in MS.


Self-Monitoring App Preferences for Sun Protection: Discrete Choice Experiment Survey Analysis.
The availability and use of health apps continues to increase, revolutionizing the way mobile health interventions are delivered. Apps are increasingly used to prevent disease, improve well-being, and promote healthy behavior. On a similar rise is the incidence of skin cancers. Much of the underlying risk can be prevented through behavior change and adequate sun protection. Self-monitoring apps have the potential to facilitate prevention by measuring risk (eg, sun intensity) and encouraging protective behavior (eg, seeking shade). Our aim was to assess health care consumer preferences for sun protection with a self-monitoring app that tracks the duration and intensity of sun exposure and provides feedback on when and how to protect the skin. We conducted an unlabeled discrete choice experiment with 8 unique choice tasks, in which participants chose among 2 app alternatives, consisting of 5 preidentified 2-level attributes (self-monitoring method, privacy control, data sharing with health care provides, reminder customizability, and costs) that were the result of a multistep and multistakeholder qualitative approach. Participant preferences, and thus, the relative importance of attributes and their levels were estimated using conditional logit modeling. Analyses consisted of 200 usable surveys, yielding 3196 observations. Our respondents strongly preferred automatic over manually operated self-monitoring (odds ratio [OR] 2.37, 95% CI 2.06-2.72) and no cost over a single payment of 3 Swiss francs (OR 1.72, 95% CI 1.49-1.99). They also preferred having over not having the option of sharing their data with a health care provider of their choice (OR 1.66, 95% CI 1.40-1.97), repeated over single user consents, whenever app data are shared with commercial thirds (OR 1.57, 95% CI 1.31-1.88), and customizable over noncustomizable reminders (OR 1.30, 95% CI 1.09-1.54). While most participants favored thorough privacy infrastructures, the attribute of privacy control was a relatively weak driver of app choice. The attribute of self-monitoring method significantly interacted with gender and perceived personal usefulness of health apps, suggesting that female gender and lower perceived usefulness are associated with relatively weaker preferences for automatic self-monitoring. Based on the preferences of our respondents, we found that the utility of a self-monitoring sun protection app can be increased if the app is simple and adjustable; requires minimal effort, time, or expense; and has an interoperable design and thorough privacy infrastructure. Similar features might be desirable for preventive health apps in other areas, paving the way for future discrete choice experiments. Nonetheless, to fully understand these preference dynamics, further qualitative or mixed method research on mobile self-monitoring-based sun protection and broader preventive mobile self-monitoring is required. RR2-10.2196/16087.


Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury.
Cerebrovascular reactivity to CO(2) or hypotension was studied in vivo and in vitro [pressurized arteries ( approximately 82 micrometer) and arterioles ( approximately 30 micrometer)] at 1 h after mild controlled cortical impact (CCI) injury in rats. The cortical perfusion response [assessed using laser-Doppler flowmetry (LDF)] to altered CO(2) was diminished (up to 81%) after mild CCI injury. The responses to CO(2) alterations in arteries and arterioles isolated from the injured cortex were similar to responses in vessels isolated from sham-injured animals. After mild CCI injury, the autoregulatory response to hypotension (measured using LDF) was maintained or even enhanced, depending on the method used to measure the response. Vessels isolated from the injury site showed a response to changes in pressure similar to that in vessels isolated from sham-injured rats. We conclude that mild CCI injury produces complicated alterations in cerebrovascular control. Whereas the autoregulatory response to hypotension was maintained or even enhanced, the in vivo vascular response to CO(2) was severely compromised. The altered response to CO(2) was not caused by an intrinsic vascular perturbation but rather an altered milieu after mild CCI injury.


[Iodine, carbohydrate and protein metabolism in rats with cobalt deficiency].
Experiments on male rats maintained at the diet with a low amount of cobalt have revealed a decrease in values of iodine indices in organs and tissues except for the liver tissues where a sharp increase in the inorganic iodine concentration as well as disturbances of the protein and carbohydrate metabolism were observed. Mathematical analysis has shown a high correlation of changes in the carbohydrate and protein metabolism and concentration of protein-bound iodine in blood. It has permitted a conclusion on an indirect effect of the cobalt deficiency on the metabolism processes as a result of changes in the concentration of protein-bound iodine in blood and tissues.


Current digital imaging for the otolaryngologist.
Digital imaging has arrived as a standard tool for the otolaryngologist. There is no better evidence of this than the American Academy of Otolaryngology-Head and Neck Surgery moving to an all-digital format for its 2003 national meeting. No longer will 35-mm slide projectors be available for any presentations in the country's largest otolaryngology program. Also, all of the major journals in the field now accept or require digital files of illustrations and photographs. With this change in standard, the question is no longer if, or even when to incorporate digital imaging techniques, but how to do so most efficiently. This can be quite a challenge, given the ever-changing field of computer technology. This article is intended to introduce the fundamentals of digital imaging, and how this technology can best be integrated into an otolaryngology practice.


Regulation of Vascular Tone, Angiogenesis and Cellular Bioenergetics by the 3-Mercaptopyruvate Sulfurtransferase/H2S Pathway: Functional Impairment by Hyperglycemia and Restoration by DL-α-Lipoic Acid.
Hydrogen sulfide (H2S), as a reducing agent and an antioxidant molecule, exerts protective effects against hyperglycemic stress in the vascular endothelium. The mitochondrial enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is an important biological source of H2S. We have recently demonstrated that 3-MST activity is inhibited by oxidative stress in vitro and speculated that this may have an adverse effect on cellular homeostasis. In the current study, given the importance of H2S as a vasorelaxant, angiogenesis stimulator and cellular bioenergetic mediator, we first determined whether the 3-MST/H2S system plays a physiological regulatory role in endothelial cells. Next, we tested whether a dysfunction of this pathway develops during the development of hyperglycemia and μmol/L to diabetes-associated vascular complications. Intraperitoneal (IP) 3-MP (1 mg/kg) raised plasma H2S levels in rats. 3-MP (10 1 mmol/L) promoted angiogenesis in vitro in bEnd3 microvascular endothelial cells and in vivo in a Matrigel assay in mice (0.3-1 mg/kg). In vitro studies with bEnd3 cell homogenates demonstrated that the 3-MP-induced increases in H2S production depended on enzymatic activity, although at higher concentrations (1-3 mmol/L) there was also evidence for an additional nonenzymatic H2S production by 3-MP. In vivo, 3-MP facilitated wound healing in rats, induced the relaxation of dermal microvessels and increased mitochondrial bioenergetic function. In vitro hyperglycemia or in vivo streptozotocin diabetes impaired angiogenesis, attenuated mitochondrial function and delayed wound healing; all of these responses were associated with an impairment of the proangiogenic and bioenergetic effects of 3-MP. The antioxidants DL-α-lipoic acid (LA) in vivo, or dihydrolipoic acid (DHLA) in vitro restored the ability of 3-MP to stimulate angiogenesis, cellular bioenergetics and wound healing in hyperglycemia and diabetes. We conclude that diabetes leads to an impairment of the 3-MST/H2S pathway, and speculate that this may contribute to the pathogenesis of hyperglycemic endothelial cell dysfunction. We also suggest that therapy with H2S donors, or treatment with the combination of 3-MP and lipoic acid may be beneficial in improving angiogenesis and bioenergetics in hyperglycemia.


[Health related quality of life: Conceptual elements].
Health related Quality of Life is commonly used as a subjective assessment of health status. This article is a review of theoretical concepts about quality of life. Some models are proposed and general issues about it measurement are analyzed. Information about health related quality of life helps for decision making about health care both in clinical and public care settings.


Early Life Adversity and Polygenic Risk for High Fasting Insulin Are Associated With Childhood Impulsivity.
While the co-morbidity between metabolic and psychiatric behaviors is well-established, the mechanisms are poorly understood, and exposure to early life adversity (ELA) is a common developmental risk factor. ELA is associated with altered insulin sensitivity and poor behavioral inhibition throughout life, which seems to contribute to the development of metabolic and psychiatric disturbances in the long term. We hypothesize that a genetic background associated with higher fasting insulin interacts with ELA to influence the development of executive functions (e.g., impulsivity in young children). We calculated the polygenic risk scores (PRSs) from the genome-wide association study (GWAS) of fasting insulin at different thresholds and identified the subset of single nucleotide polymorphisms (SNPs) that best predicted peripheral insulin levels in children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort [N = 467; p t- initial = 0.24 (10,296 SNPs), p t- refined = 0.05 (57 SNPs)]. We then calculated the refined PRS (rPRS) for fasting insulin at this specific threshold in the children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort and investigated its interaction effect with adversity on an impulsivity task applied at 36 months. We found a significant effect of interaction between fasting insulin rPRS and adversity exposure predicting impulsivity measured by the Snack Delay Task at 36 months [β = -0.329, p = 0.024], such that higher PRS [β = -0.551, p = 0.009] was linked to more impulsivity in individuals exposed to more adversity. Enrichment analysis (MetaCoreTM) of the SNPs that compose the fasting insulin rPRS at this threshold was significant for certain nervous system development processes including dopamine D2 receptor signaling. Additional enrichment analysis (FUMA) of the genes mapped from the SNPs in the fasting insulin rPRS showed enrichment with the accelerated cognitive decline GWAS. Therefore, the genetic background associated with risk for adult higher fasting insulin moderates the impact of early adversity on childhood impulsivity.


Graphene aerogel/epoxy composites with exceptional anisotropic structure and properties.
3D interconnected graphene aerogels (GAs) are prepared through one-step chemical reduction and rational assembly of graphene oxide (GO) sheets, so that the difficulties to uniformly disperse the individual graphene sheets in the polymer matrixes are avoided. Apart from ultralow density, high porosity, high electrical conductivity, and excellent compressibility, the resulting GAs possess a cellular architecture with a high degree of alignment when the graphene content is above a threshold, ∼0.5 wt %. The composites prepared by infiltrating GA with epoxy resin present excellent electrical conductivities, together with high mechanical properties and fracture toughness. The unusual anisotropic structure gives rise to ∼67% and ∼113% higher electrical conductivity and fracture toughness of the composites, respectively, in the alignment direction than that transverse to it.


Modulation of ACTH-induced cortisol release by polyunsaturated fatty acids in interrenal cells from gilthead seabream, Sparus aurata.
Highly unsaturated fatty acids are essential components of cellular membranes of vertebrates and can modulate physiological processes, including membrane transport, receptor function and enzymatic activities. In gilthead sea bream, dietary deficiencies of essential fatty acids of marine fish raise the basal cortisol levels and alter the pattern of cortisol release after stress. The aim of the present study was to clarify the effect of different essential fatty acids on adrenocorticotropic hormone (ACTH)-induced cortisol production and release in fish, through in vitro studies of sea bream interrenal cells maintained in superfusion and incubated with different types of fatty acids and eicosanoid production inhibitors. Results showed the first evidence of the effect of certain fatty acids on cortisol production by ACTH-stimulated interrenal cells in fish. Both arachidonic acid (ARA) and particularly eicosapentaenoic acid (EPA) promoted cortisol production in sea bream interrenal cells. Moreover, incubation with indometacin (INDO) reduced the increased cortisol production induced by EPA and ARA, suggesting mediation by their cyclooxygenase-derived products. Docosahexaenoic acid stimulated cortisol production to a lesser extent than that caused by EPA or ARA, but the inhibitory effect of INDO was not as marked as it was for the other fatty acids. In contrast, supplementation with dihomogammalinolenic acid reduced cortisol production, denoting the inhibitor effect of this fatty acid in cortisol secretion.


An increased concentration of receptor activator of nuclear factor kappa-B ligand pre-dates the onset of rheumatoid arthritis.
RANK ligand (RANKL) is involved in destruction and osteoporosis in RA. In this study, the relationships between RANKL and ACPA, anti-carbamylated protein antibodies (anti-CarP), cytokines and chemokines were analysed in individuals before the onset of RA symptoms, and their associations with radiological findings at disease onset were assessed. This was a case-control study performed within the Medical Biobank of Northern Sweden that included 470 pre-symptomatic individuals [334 women and 136 men; mean (s.d.) age 52.3 (9.4) years] using blood samples donated before symptom onset (pre-dating time; 5.0 years) and 96 controls (60 women and 36 men). Plasma was analysed for RANKL (BioVendor, Karasek, Brno, Czech Republic), anti-CCP2 antibodies (Eurodiagnostics, Malmö, Sweden), anti-CarP antibodies (in-house ELISA), ACPA specificities (ISAC-platform, Phadia AB, Uppsala, Sweden) and cytokines/chemokines (Meso Scale Discovery methods, Rockville, MD, USA). Radiographs of hands and feet were graded using the Larsen score. The concentration of RANKL was higher in the pre-symptomatic individuals compared with controls; mean (s.e.m.): 0.50 (0.03) vs 0.22 (0.02) nmol/l (P < 0.001). The concentration increased gradually over time until symptom onset but appeared later than ACPA/RF/anti-CarP antibodies. Positivity for these antibodies yielded higher levels of RANKL compared with seronegativity (P < 0.001). RANKL concentrations were significantly associated with IL-6 and IL-10 concentrations. The combination of positivity for RANKL and anti-CarP antibodies resulted in a higher Larsen score at diagnosis β = 6.18 (95% CI: 0.93, 11.43; P = 0.022). RANKL concentrations were increased several years before symptom onset for RA, particularly in ACPA/RF/anti-CarP-positive individuals, all detectable earlier than RANKL. Positivity for RANKL and anti-CarP antibodies yielded the highest Larsen score at disease onset.


[The pharmacological effect of betapressin in hypertension].
The work analyses the results of treating 20 hypertensive patients with (stage I-II) with betapressin. The drug is shown to be active in causing a significant decrease of systolic and mean arterial pressure. Its hypotensive effect is associated with essential decrease of peripheral vascular resistance. This circumstance, as well as acceleration of the heart rhythm, leads to increase of the cardiac output. Betapressin is recommended for monotherapy of patients suffering from stages I-II hypertension with eu- and hypokinetic types of hemodynamics.


[Pathological anatomy of thymus gland tumors].
The paper presents detailed morphological characteristics of 31 thymomas and 25 microscopically similar neoplasias of the anterior mediastinum (carcinoid, seminoma, lymphogranulomatosis, angiofollicular lymphoma, etc). The term "thymoma" is determined as a tumour consisting of two components: mandatory epithelial one and lymphocytes. The diversity of the morphological picture of thymomas is determined mainly by the variability of the epithelial component. The special features of the ultrastructural organization of thymomas (the presence of desmosomes, tonofibrils and basal membrane) were revealed which facilitate the differential diagnosis of the anterior mediastinum tumours.


Pathological validation of a CT-based scale for subcortical vascular disease. The OPTIMA Study.
The validity of a computed tomography (CT)-based rating scale that separately rates leukoaraiosis, patchy lesions, and lacunes was tested using neuropathological findings collected on 87 subjects enrolled in the Oxford Project to Investigate Memory and Ageing. The CT-based score (range 0-64) was associated with both small vessel disease (p = 0.015) and microinfarcts (p = 0.002) on pathology. A sum score of subcortical cerebrovascular disease (CVD) on pathology was computed, 0 indicating absent/mild small vessel CVD and no microinfarcts, 1 moderate small vessel CVD or microinfarcts, and 2 and higher both conditions or severe small vessel CVD. Subjects with a sum score of 0 were decreasing with increasing severity of CT-based score (64, 46, and 25% in those with CT-based scores of 0, 1-38, and 39 and higher), while those with a sum score of 2 and higher were increasing (0, 14, and 44%; p = 0.002). A standardized assessment of subcortical CVD on CT films can be compounded into a unique score that is in good agreement with neuropathology. This supports the validity of the CT-based visual rating scale as a valid tool to detect subcortical vascular changes in elderly persons.


Walking football for Health - physiological response to playing and characteristics of the players.
Walking Football (WF) is one type of recreational football increasing in popularity, targeting older adults. Further knowledge on the intensity and physical workload of WF, characteristics of the players, the social context, and reasons for playing WF is needed. Thus, the aim of the study was to characterize the individuals that regularly play WF and their experience of WF, and the physiological characteristics of the sport. Sixty-three players from three clubs taking part in organised WF in Sweden were included. The players participated in up to four WF-games and underwent performance tests and answered a questionnaire. The participants mean age was 70.9 years, ranging from 63 to 85 years with 71% (n = 27) of the men and 68% (n = 13) of the women having a BMI > 25. Fifty-one percent (n = 27) of the players had hypertension, and 73% (n = 39) regularly used prescription drugs due to illness. During WF, the players covered on average 2,409 m (2,509 m for men and 2,205 m for women, p = .001). Expressed in percentage of their age-estimated maximal heart rate, mean heart rate represented 80 ± 9 and 80 ± 8% of max for men, and 78 ± 9 and 79 ± 9% of max for women in the first and second halves, respectively, hence WF can be considered a moderate intensity activity for older adults. The main reason for WF participation was to socialize. WF includes a considerable number of accelerations and decelerations, making it more energetically and mechanically demanding than walking.


Cortisol resistance in acquired immunodeficiency syndrome.
This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.


Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.
As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo.


Internet-delivered exposure-based treatment vs. stress management for irritable bowel syndrome: a randomized trial.
Our research group has developed an internet-delivered cognitive behavioral treatment (ICBT) for irritable bowel syndrome (IBS). We compared ICBT with internet-delivered stress management (ISM) for IBS to assess whether the effects of ICBT are specific. This was a randomized controlled trial, including 195 self-referred participants diagnosed with IBS. The treatment interventions lasted for 10 weeks and included an online therapist contact. The ICBT emphasized acceptance of symptoms through exposure to IBS symptoms and related negative feelings. The ICBT also included mindfulness training. The ISM emphasized symptom control through relaxation techniques, dietary adjustments, and problem-solving skills. Severity of IBS symptoms was measured with the gastrointestinal symptom rating scale-IBS version (GSRS-IBS). Credibility of the treatments and expectancy of improvement were assessed with the treatment credibility scale. The participants' perceived therapeutic alliance with their online therapist was measured with the working alliance inventory. At post-treatment and 6-month follow-up, 192 (99%) and 169 (87%) participants returned data, respectively. At post-treatment and 6-month follow-up, we found significant differences on the GSRS-IBS, favoring ICBT. The difference on GSRS-IBS scores was 4.8 (95% confidence interval (CI): 1.2-8.4) at post-treatment and 5.9 (95% CI: 1.9-9.9) at 6-month follow-up. There were no significant differences on the treatment credibility scale or the working alliance inventory between the groups. Internet-delivered CBT has specific effects that cannot be attributed only to treatment credibility, expectancy of improvement, therapeutic alliance, or attention. Furthermore, a treatment based on exposure exercises specifically tailored for IBS may be a better treatment option than general stress and symptom management for IBS patients. ICBT is a promising treatment modality for IBS as it can be offered to IBS patients in much larger scale than conventional psychological treatments.


Sexuality and the older woman.
Sexual health is a key public health issue. The older woman faces a number of changes to her sexual health, wellbeing and sexuality. These changes result in many older women having to adapt to a series of complex transitions that can be challenging. This article aims to identify and explore some of these changes and how they can have a significant impact on women's quality of life. Nurses play an important role in assessing and helping women to manage normal and pathological age-related changes in order to improve the sexual health of older women and ensure they receive the advice and support needed at this stage of their life.


X-ray chemical imaging and the electronic structure of a single nanoplatelet Ni/graphene composite.
Chemical imaging and quantitative analysis of a single graphene nanoplatelet grown with Ni nanoparticles (Ni/graphene) has been performed by scanning transmission X-ray microscopy (STXM). Local electronic and chemical structure of Ni/graphene has been investigated by spatially resolved C, O K-edges and Ni L-edge X-ray absorption near edge structure (XANES) spectroscopy, revealing the covalent anchoring of Ni(0) on graphene. This study facilitates the understanding of the structure modification of host materials for hydrogen storage and offers a better understanding of interaction between Ni particles and graphene.


Do Peers, Neighborhood Disorder, Religiosity, Spirituality, and Family Support Influence Polysubstance Use Among Older Youth Transitioning from Foster Care?
Few studies have explored polysubstance use among youths aging out of foster care, despite higher rates of substance misuse for youths exiting foster care than those in the general population. Polysubstance use has been linked to substance use disorders, health problems, cognitive impairment, suicide, and overdose. This study investigates understudied risk and protective factors associated with polysubstance use with data from 384 youth who turned 17 years old between December 1, 2001, and June 30, 2003, and were transitioning out of foster care from the Missouri Children's Division. We conducted bivariate analyses with chi-square tests for categorical variables and Analysis of Variance with continuous independent variables. Then we conducted a multinomial logistic regression to explore differences between individuals who used 1 or no substances, individuals who used only alcohol and marijuana, and individuals who used 2 or more substances. Bivariate analyses found that being white, having deviant peers, and living in a more disordered neighborhood were risk factors for polysubstance use. Multinomial logistic regression results found that being white (RR = 6.89, p < .001), having deviant peers (RR = 1.15, p < .001), and living in a more disordered neighborhood (RR = 1.13, p < .05), increased the risk engaging in polysubstance use. Similar to findings in other studies, we found that deviant peers and neighborhood disorder increase the risk of polysubstance use, but family support, church attendance, and spirituality were not protective against polysubstance use. Interventions should work to reduce deviant peer relationships among foster youth.


Evaluation of a Dementia Education Program for Family Medicine Residents.
Dementia diagnosis and management is increasing in importance in the training of future family physicians. This study evaluated the impact of a dementia education program for family medicine residents (FMR) on residents' knowledge, attitudes, and confidence with respect to dementia assessment and management. A three-part questionnaire was developed and validated for these purposes. A mixed methods study design was employed. The questionnaire's internal consistency and test-retest reliability was determined and content validity was assessed. Twelve FMR participated in questionnaire validation. Program participants completed the validated questionnaire at baseline, at interim, and following program completion. Twenty-seven FMR completed the questionnaire as part of the program evaluation. Willing residents also participated in program feedback interviews. Differences in questionnaire scores between program participants and the comparison group were examined. Each questionnaire component demonstrated high internal consistency (Cronbach's α: 0.83-0.91) and test-retest reliability (intraclass correlation coefficients: 0.74-0.91). Program participants (n = 15) scored significantly higher than the comparison group (n = 12) on the knowledge component and also reported greater confidence in several areas. Qualitative data indicated that residents felt the program focused on important topic areas and appreciated the opportunity to work in an interprofessional team. Evaluation results indicate that the program improved FMRs' knowledge on dementia assessment and management, as well as increased the residents' confidence levels.


Nucleoside analogue therapy following one-year course of hepatitis B immunoglobulin in preventing hepatitis B virus reactivation after living donor liver transplantation.
The combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside analogue is well tolerated for the hepatitis B recipients after liver transplantation, but its cost is an important problem in these days. Here we report the efficacy of nucleoside analogue therapy following one-year course of HBIG plus nucleoside analogue after living donor liver transplantation (LDLT). Out of 103 LDLTs, we selected 14 recipients who received the post-transplant therapy against reactivation of hepatitis B virus for more than 30 months. Those were eight patients with chronic hepatitis B, three with fulminant hepatitis, and three whose donors were positive for antibody to HB core antigen (HBc). During two days after the operation, HBIG (40,000 units) was administered, and the serum level of antibody to HB surface antigen (HBs) was maintained at around 150 IU/L for one year by monthly administration of HBIG. After one year, HBIG was withdrawn. A nucleoside analogue was administered daily from just after LDLT, and it was continued up to the present. Among the 14 patients, two recipients had recurrence of hepatitis B. Three patients, including one patient with recurrence of hepatitis B, died due to hepatocellular carcinoma or its associated cirrhosis; namely, their deaths are unrelated to hepatitis B-related diseases. The remaining 11 patients are leading normal lives. In conclusion, nucleoside analogue therapy after one-year course of HBIG plus nucleoside analogue is feasible and cost-effective in preventing HBV reactivation. But the patients are still at risk of breakthrough and some patients may need continued prophylaxis with HBIG.


Juglanin alleviates bleomycin-induced lung injury by suppressing inflammation and fibrosis via targeting sting signaling.
Idiopathic pulmonary fibrosis (IPF), characterized by excessive collagen deposition, is a progressive and typically fatal lung disease without effective therapeutic strategies. Juglanin, as a natural product mainly isolated from green walnut husks of Juglans mandshuric, has various bioactivities, including anti-oxidative, anti-inflammatory and anti-fibrotic effects. Stimulator of interferon genes (Sting) is a signaling molecule and plays an essential role in meditating fibrosis. However, the effects of Jug and Sting on pulmonary fibrosis are not fully understood. In this study, we investigated the role of Jug in bleomycin (BLM)-induced inflammation and fibrosis mouse model, as well as the underlying molecular mechanism. The results here indicated that Jug-treated mice exhibited a definitively improved survival rate than that of the BLM-challenged mice. Jug administration significantly alleviated neutrophil alveolar infiltration, lung vascular permeability and pro-inflammatory response in BLM mice. Subsequently, the pulmonary fibrosis induced by BLM was markedly attenuated by Jug through reducing the expression of fibrotic hallmarks, including transforming growth factor-β1 (TGF-β1), fibronectin, matrix metallo-proteinase-9 (MMP-9), α-smooth muscle actin (α-SMA) and collagen I. Importantly, we found that BLM mice showed higher expression levels of Sting in lung tissues, which were notably restrained by Jug treatment. The role of Jug in suppressing Sting was confirmed in TGF-β-incubated cells. Notably, the in vitro analysis further showed that Sting knockdown could ameliorate TGF-β-triggered collagen accumulation. In contrast, TGF-β-induced fibrosis was accelerated by Sting over-expression. Therefore, BLM may induce lung fibrosis through activating Sting signaling, and Jug could be used therapeutically to improve tissue repair and attenuate the intractable disease.


Impact of administered bifidobacterium on murine host fatty acid composition.
Recently, we reported that administration of Bifidobacteria resulted in increased concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in murine adipose tissue [1]. The objective of this study was to assess the impact of co-administration of Bifidobacterium breve NCIMB 702258 and the substrate for EPA, alpha-linolenic acid, on host fatty acid composition. alpha-Linolenic acid-supplemented diets (1%, wt/wt) were fed to mice (n = 8), with or without B. breve NCIMB 702258 (daily dose of 10(9) microorganisms) for 8 weeks. Two further groups received either supplement of B. breve alone or unsupplemented diet. Tissue fatty acid composition was assessed by gas liquid chromatography. Dietary supplementation of alpha-linolenic acid resulted in higher (P < 0.05) alpha-linolenic acid and EPA concentrations in liver and adipose tissue and lower (P < 0.05) arachidonic acid in liver, adipose tissue and brain compared with mice that did not receive alpha-linolenic acid. Supplementation with B. breve NCIMB 702258 in combination with alpha-linolenic acid resulted in elevated (P < 0.05) liver EPA concentrations compared with alpha-linolenic acid supplementation alone. Furthermore, the former group had higher (P < 0.05) DHA in brain compared with the latter group. These results suggest a role for interactions between fatty acids and commensals in the gastrointestinal tract. This interaction between administered microbes and fatty acids could result in a highly effective nutritional approach to the therapy of a variety of inflammatory and neurodegenerative conditions.