Retaining older experienced nurses in the Northern Territory of Australia: a qualitative study exploring opportunities for post-retirement contributions.
Many countries are facing an ageing of the nursing workforce and increasing workforce shortages. This trend is due to members of the 'baby boomer' generation leaving the workforce for retirement and a declining pool of younger people entering the nursing profession. New approaches to engaging older nurses in the workforce are becoming common in nursing globally but have yet to be adapted to remote contexts such as the Northern Territory (NT) of Australia. This article reports findings from a qualitative study of 15 participants who explored perceived opportunities for and barriers to implementing flexible strategies to engage older nurses in the NT workforce after they resign from full-time work. The study used a descriptive qualitative design. Data were collected using semi-structured interviews with NT nurses approaching retirement (six nurses aged 50 years and over) and their managers (n=9). Clinicians were employed in practice settings that included hospitals, community health and 'Top End' (north of and including the town of Katherine), as well as Central Australian remote area communities. One participant who was employed as primary health centre manager in a remote community also held a clinical role. Managers were employed in both senior and line management positions in community and remote health as well as NT hospitals. Three major themes emerged from the data. First, interview participants identified potential for flexible post-retirement engagement of older nurses and a range of concrete engagement opportunities 'on and off the floor' were identified. Second, the main barriers to post-retirement engagement were an existing focus on the recruitment of younger Australian and overseas-trained nurses, and the remoteness of nursing practice settings from the residential locations of retired nurses. Third, existing informal system of post-retirement working arrangements, characterized by ad hoc agreements between individual nurses and managers, is poorly suited to scaling up. A knowledge and change-management approach is required to change employers' views of the value of older nurses. Better engagement of those nurses may assist the NT Department of Health address the severe nursing workforce shortages and prevent the loss of significant remote area nursing knowledge.


Similarities and differences in intrapopulation trait correlations of co-occurring tree species: consistent water-use relationships amid widely different correlation patterns.
General relationships among functional traits have been identified across species, but the forces shaping these relationships remain largely unknown. Adopting an approach from evolutionary biology, we studied similarities and differences in intrapopulation trait correlations among locally co-occurring tree species to assess the roles of constraints, phylogeny, and the environmental niche in shaping multivariate phenotypes. We tested the hypotheses (1) that intrapopulation correlations among functional traits are largely shaped by fundamental trade-offs or constraints and (2) that differences among species reflect adaptation to their environmental niches. We compared pairwise correlations and correlation matrices of 17 key functional traits within and among temperate tree species. These traits describe three well-established trade-off dimensions characterizing interspecific relationships among physiological functions: resource acquisition and conservation; sap transport and mechanical support; and branch architecture. Six trait pairs are consistently correlated within populations. Of these, only one involves dimensionally independent traits: LMA-δ13 C. For all other traits, intrapopulation functional trait correlations are weak, are species-specific, and differ from interspecific correlations. Species intrapopulation correlation matrices are related to neither phylogeny nor environmental niche. The results (1) suggest that the functional design of these species is centered on efficient water use, (2) highlight flexibility in plant functional design across species, and (3) suggest that intrapopulation, local interspecific, and global interspecific correlations are shaped by processes acting at each of these scales.


Defining hepatic dysfunction parameters in two models of fatty liver disease in zebrafish larvae.
Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepatocytes and dilation of hepatic vasculature occurred only in ethanol-treated larvae. Hepatic stellate cells (HSCs) become activated during liver injury and HSC numbers increased in both models. Whether the excess lipids in hepatocytes are a direct cause of hepatocyte dysfunction in fatty liver disease has not been defined. We prevented ethanol-induced steatosis by blocking activation of the sterol response element binding proteins (Srebps) using gonzo(mbtps1) mutants and scap morphants and found that hepatocyte dysfunction persisted even in the absence of lipid accumulation. This suggests that lipotoxicity is not the primary cause of hepatic injury in these models of fatty liver disease. This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration.


Achieving Low-Energy Driven Viologens-Based Electrochromic Devices Utilizing Polymeric Ionic Liquids.
Herein, three kinds of viologens-based electrochromic devices (ECDs) (heptyl viologen (HV(BF4)2), octyl viologen (OV(BF4)2), and nonyl viologen (NV(BF4)2)) were fabricated utilizing ferrocene (Fc) as a redox mediator. Among them, the NV(BF4)2-based ECD exhibits the highest coloration efficiency (36.2 cm2/C) owing to the lowest driving energy. Besides, switching between 0 and 1.2 V, the NV(BF4)2-based ECD shows a desirable initial transmittance change (ΔT = 56.7% at 605 nm), and long-term stability (ΔT = 45.4% after 4000 cycles). Furthermore, a UV-cured polymer electrolyte containing polymeric ionic liquid (PIL, 1-allyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and ethoxylated trimethylolpropane triacrylate (ETPTA) was introduced to the NV(BF4)2-based ECD. By controlling the weight percentage of the PIL, different curing degrees of the polymer electrolytes were obtained and led to an improved stability of the NV(BF4)2-based ECD because of the immobilization of NV(BF4)2. This observation was explained by calculating the apparent diffusivity (Dapp) of the redox species in the NV(BF4)2-based ECD under various curing degrees. In addition, increasing the amount of PIL leads to a lower driven energy needed for the NV(BF4)2-based ECD, following the same trend as the value of Dapp. Among all NV(BF4)2-based ECDs, 20 wt % of PIL addition (20-PIL ECD) exhibits large transmittance change (ΔT = 55.2% at 605 nm), short switching times (2.13 s in coloring and 2.10 s in bleaching), high coloration efficiency (60.4 and 273.5 cm2/C at 605 nm, after excluding the current density at the steady state), and exceptional cycling stability (ΔT = 53.8% after 10,000 cycles, or retained 97.5% of its initial ΔT).


Production of Low-Potassium Content Melon Through Hydroponic Nutrient Management Using Perlite Substrate.
Chronic kidney disease patients are restricted to foods with high potassium content but our daily diets including melon are rich in potassium. Therefore, we investigated the production of low-potassium melon through hydroponic nutrient management in soilless culture using perlite substrate during autumn season of 2012, 2014 and spring season of 2016. In the first study, melon plants were supplied with 50% standard 'Enshi' nutrient solution until first 2 weeks of culture. In 3rd and 4th week, amount of applied potassium was 50, 75, 100, and 125% of required potassium nitrate for each plant per week (based on our previous study). It was found that, melon plants grown with 50% of its required potassium nitrate produced fruits with about 53% low-potassium compared to control. In the following study, four cultivars viz. Panna, Miyabi shunjuukei, Miyabi akifuyu412, and Miyabi soushun banshun309 were evaluated for their relative suitability of low-potassium melon production. Results showed insignificant difference in fruit potassium content among the cultivars used. Source of potassium fertilizer as potassium nitrate and potassium sulfate and their restriction (from 1 or 2 weeks after anthesis) were also studied. There were no influences on fruit potassium content and yield due to sources of potassium fertilizer and restriction timings. In our previous studies, it was evident that potassium can be translocated from leaves to fruits at maturity when it was supplied nutrient without potassium. Thus, we also studied total number of leaves per plant (23, 24, 25, 26, and 27 leaves per plant). It was evident that fruit potassium, yield, and quality were not influenced significantly due to differences in number of leaves per plant. These studies showed that restriction of potassium nitrate in the culture solution from anthesis to harvest could produce melon fruits with low-potassium (>20%) content compared to potassium content of greenhouse grown melon (340 mg/100 g FW). Quality testing and clinical validation of low-potassium melon also showed positive responses compared to greenhouse grown melon.


Randomized-controlled trial of a modified Mediterranean dietary program for multiple sclerosis: A pilot study.
There is a high level of interest in the potential role of diet among the MS community. There is a limited level of evidence for a Mediterranean-style dietary pattern in MS; the feasibility of conducting studies using educational tools to deliver this type of intervention and study its effects is unknown. To establish clinical trial feasibility for future studies utilizing educational delivery of a dietary intervention in MS; to explore the effects of a modified Mediterranean dietary intervention in MS. We randomly assigned women with MS to follow/not follow the prescribed modified Mediterranean dietary intervention for 6 months, delivered through educational sessions. The diet encouraged the intake of fish and other foods high in poly- and monounsaturated fats, fresh fruits, vegetables, and whole grains and eliminated meat, dairy, and most processed foods and limited salt intake to <2 g/day. Primary endpoints related to meeting target enrollment within the specified time frame, adherence, and study completion. Clinical endpoints were evaluated in an exploratory fashion. We screened 128 potential participants and enrolled 36 within 9 months, surpassing target enrollment of 30 participants at a single center in 1 year. Self-reported adherence was excellent (90.3%), with an overall study completion rate of 94.4%. The intervention group exhibited a statistically significant decline in the trajectory of Neurological Fatigue Index-MS scores (p = 0.01), a trend toward reduced Multiple Sclerosis Impact Scale-29 scores that became significant after outlier removal (p = 0.12; p = 0.023), and a reduction in Expanded Disability Status Scale (p = 0.01) over time as compared to the non-intervention group. It is reasonable to expect a high level of interest and commitment to this type of dietary intervention study in MS, and feasible to deliver it purely through education in a clinical setting with high adherence levels despite restrictive requirements. In this pilot study, a modified Mediterranean dietary intervention reduced fatigue, impact of MS symptoms, and disability. Further work is needed.


Rearrangement of simian virus 40 regulatory region is not required for induction of progressive multifocal leukoencephalopathy in immunosuppressed rhesus monkeys.
Rearrangements of the JC virus (JCV) regulatory region (RR) are consistently found in the brains of patients with progressive multifocal leukoencephalopathy (PML), whereas the archetype RR is present in their kidneys. In addition, the C terminus of the large T antigen (T-Ag) shows greater variability in PML than does the rest of the coding region. To determine whether similar changes in simian virus 40 (SV40) are necessary for disease induction in monkeys, we sequenced the SV40 RR and the C terminus of the T-Ag from the brain of simian/human immunodeficiency virus (SHIV)-infected monkey 18429, which presented spontaneously with an SV40-associated PML-like disease, as well as from the peripheral blood mononuclear cells (PBMC), kidneys, and brains of SV40-seronegative, SHIV-infected monkeys 21289 and 21306, which were inoculated with the 18429 brain SV40 isolate. These animals developed both SV40-associated PML and meningoencephalitis. Thirteen types of SV40 RR were characterized. Compared to the SV40 archetype, we identified RRs with variable deletions in either the origin of replication, the 21-bp repeat elements, or the late promoter, as well as deletions or duplications of the 72-bp enhancer. The archetype was the most prominent RR in the brain of monkey 18429. Shortly after inoculation, a wide range of RRs could be found in the PBMC of monkeys 21289 and 21306. However, the archetype RR became the predominant type in their blood, kidneys, and brains at the time of sacrifice. On the contrary, the T-Ag C termini remained identical in all compartments of the three animals. These results indicate that unlike JCV in humans, rearrangements of SV40 RR are not required for brain disease induction in immunosuppressed monkeys.


Worsening Hypoxemia in the Face of Increasing PEEP: A Case of Large Pulmonary Embolism in the Setting of Intracardiac Shunt.
BACKGROUND Patent foramen ovale (PFO) are common, normally resulting in a left-to-right shunt or no net shunting. Pulmonary embolism (PE) can cause sustained increased pulmonary vascular resistance (PVR) and right atrial pressure. Increasing positive end-expiratory pressure (PEEP) improves oxygenation at the expense of increasing intrathoracic pressures (ITP). Airway pressure release ventilation (APRV) decreases shunt fraction, improves ventilation/perfusion (V/Q) matching, increases cardiac output, and decreases right atrial pressure by facilitating low airway pressure. CASE REPORT A 40-year-old man presented with dyspnea and hemoptysis. Oxygen saturation (SaO2) 80% on room air with A-a gradient of 633 mmHg. Post-intubation SaO2 dropped to 71% on assist control, FiO2 100%, and PEEP of 5 cmH20. Successive PEEP dropped SaO2 to 60-70% and blood pressure plummeted. APRV was initaiated with improvement in SaO2 to 95% and improvement in blood pressure. Hemiparesis developed and CT head showed infarction. CT pulmonary angiogram found a large pulmonary embolism. Transthoracic echocardiogram detected right-to left intracardiac shunt, with large PFO. CONCLUSIONS There should be suspicion for a PFO when severe hypoxemia paradoxically worsens in response to increasing airway pressures. Concomitant venous and arterial thromboemboli should prompt evaluation for intra-cardiac shunt. Patients with PFO and hypoxemia should be evaluated for causes of sustained right-to-left pressure gradient, such as PE. Management should aim to decrease PVR and optimize V/Q matching by treating the inciting incident (e.g., thrombolytics in PE) and by minimizing ITP. APRV can minimize PVR and maximize V/Q ratios and should be considered in treating patients similar to the one whose case is presented here.


In situ re-endothelialization via multifunctional nanoscaffolds.
The endothelium monolayer lining in the luminal side of blood vessels provides critical antithrombotic functions. Damage to these cells will expose a highly thrombogenic subendothelium, which leads to pathological vascular changes. Using combined tissue engineering and ligand-receptor targeting strategy, we developed a biodegradable urethane-doped polyester (UPE) multifunctional targeting nanoparticle (MTN) scaffold system with dual ligands: (1) glycoprotein 1b (GP1b) to target the injured arterial endothelium and subendothelium and (2) anti-CD34 antibodies to capture endothelial progenitor cells for endothelium regeneration. The fabricated spherical MTNs of 400 nm were found to be cytocompatible and hemocompatible. Both the in vitro and ex vivo targeting of these nanoscaffolds not only showed binding specificity of MTNs onto the von Willebrand factor -coated surfaces that simulate the injured arterial walls but also competed with platelets for binding onto these injured sites. Further in vivo study has revealed that a single delivery of MTNs upon vascular injury reduced neointimal hyperplasia by 57% while increased endothelium regeneration by ∼ 60% in 21 days. These results support the promise of using MTN nanoscaffolds for treating vascular injury in situ.


Low serum folate levels as a risk factor for depressive mood in patients with chronic epilepsy.
This study takes into consideration whether low serum folate levels may contribute to depressive mood in patients with chronic epilepsy. The serum folate levels and the score on the Self-Rating Depression Scale (SDS) were examined in 46 patients with chronic epilepsy. Patients with a score indicating at least minor depression on the SDS had a significantly lower serum folate level than patients with a normal score on SDS. There was a significant negative correlation between the serum folate levels and the SDS score. A serum folate level below 7.5 ng/ml was significantly associated with a pathological score on SDS. Because a serum folate level of 7.5 ng/ml is in the normal range for many laboratories, further studies using total plasma homocysteine as a sensitive measure of functional folate deficiency are required to elucidate the impact of folate metabolism on depressive mood in patients with chronic epilepsy.


Genetic networks controlling retinal injury.
The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury. A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases. The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord. We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes.


[Surveillance on concurrent administration of quinolones and anti-inflammatory drugs in a community hospital].
Since convulsions associated with the concurrent administration of enoxacin and fenbufen were reported in 1986, the concurrent administration of quinolones and anti-inflammatory drugs has been regulated to be contraindicated or carefully administered. However, the real incidence of the co-administration is not clear. We surveyed the incidence of co-administration of these drugs from the prescriptions in a community hospital. Quinolones were prescribed in 1% of the out-patients, and anti-inflammatory drugs were co-administrated in 16% of quinolone-prescribed patients. Among quinolones prescribed, levofloxacin was used most frequently. And acetaminphen (including acetaminophen-combination) was most frequently prescribed with quinolones, and anti-inflammatory drugs, which is regulated to be carefully administrated with quinolones, were frequently co-prescribed. In medical practice, quinolones were revealed to be co-administered with anti-inflammatory drugs. Since our recent report suggests that each quinolone and each anti-inflammatory drug has different activity in their drug interaction, it should be necessary to recognize the interaction of these drugs separately for their effective and safe use in clinical field.


Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study.
Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated. A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods. Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded. Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period. Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured. After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI -30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI -33.00: -2.00)]. Immune enhancement could not be demonstrated. These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP.


The costs of home delivery of a birth dose of hepatitis B vaccine in a prefilled syringe in Indonesia.
To provide global policy-makers with decision-making information for developing strategies for immunization of infants with a birth dose of hepatitis B vaccine, this paper presents a retrospective cost analysis, conducted in Indonesia, of delivering this vaccine at birth using the Uniject prefill injection device. Incremental costs or cost savings associated with changes in the hepatitis B immunization programme were calculated using sensitivity analysis to vary the estimates of vaccine wastage rates and prices for vaccines and injection devices, for the birth dose of hepatitis B vaccine. The introduction of hepatitis B vaccine prefilled in Uniject (HB-Uniject) single-dose injection devices for use by midwives for delivering the birth dose is cost-saving when the wastage rate for multidose vials is greater than 33% (Uniject is a trademark of BD, Franklin Lakes, NJ, USA). The introduction of HB-Uniject for birth-dose delivery is economically worthwhile and can increase coverage of the critical birth dose, improve resource utilization, reduce transmission of hepatitis B and promote injection safety.


Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny.
Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5-14.5. At 3months, male progeny were left sedentary or were swim trained for 4weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males.


Peripheral blood lymphocytes as target cells of retroviral vector-mediated gene transfer.
Peripheral blood lymphocytes (PBLs) are key target cells for gene therapy of a number of inherited and acquired blood disorders. We have systematically compared four retroviral vectors, designed according to different strategies, for their efficiency in transfer and expression in human PBLs of the same reporter gene. The receptor gene used in the study codes for the human low-affinity nerve growth factor receptor (LNGFR), and is not expressed on the majority of human hematopoietic cells, thus allowing quantitative analysis of the transduced gene expression by immunofluorescence, with single cell resolution. Peripheral blood mononuclear cells (PBMCs), as well as human hematopoietic cell lines of myeloid and lymphoid origin, were transduced with the four vectors and analyzed for efficiency of gene transfer, integration and stability of vector proviruses, and LNGFR expression at both RNA and protein level. Fluorescence-activated cell sorter analysis of coexpression of LNGFR and lineage-specific cell surface markers was performed in transduced cell lines, PBLs, and T-cell clones to study gene expression on specific cell subpopulations. Although crucial differences were observed among different constructs, all retroviral vectors could transduce, under appropriate infection conditions, T-cell populations representative of the normal immune repertoire. Gene transfer and expression could be demonstrated also in circulating progenitors of mature T cells. Expression of the transduced gene was heterogeneous among cell populations infected with the different vectors, with optimal results obtained by two of the four constructs. Finally, we have devised a simple protocol based on vector-mediated gene transfer and positive immunoselection of the transduced cells that produces virtually 100% gene-modified cells. This may represent a crucial improvement in the way of designing efficacious protocols involving the use of gene-modified T lymphocytes in clinical studies.


Comparative Study Between Pre-Seasonal and Intra-Seasonal Treatment of Allergic Rhinitis Using a New 808NM Diode Laser System.
Allergic rhinitis annually reaches epidemic proportions in Japan, and represents a major problem. The application of the CO2 laser in the treatment of allergic rhinitis was first successfully reported in 1982, but CO2 laser ablation is associated with side effects. The Ohshiro Clinic started using the conventional Nd: YAG laser for the treatment of allergic rhinitis in 1993, and from 2005 we started using a diode laser-pumped Nd: YAG laser with efficacy and safety at least equal to the others. Even more recently, we have adopted a novel 808 nm diode laser, and the present retrospective study examined the difference in of the efficacy rate between the pre-seasonal and intra-seasonal treatment of allergic rhinitis with this system. One thousand, two hundred and ten patients primarily presented to the Ohshiro Clinic with allergic rhinitis during the period from December 2010 to April 2011, of whom 531 were selected for blood tests to identify 13 kinds of Japanese allergens including cedar pollen. In the 2010-2011 season, huge clouds of cedar pollen appeared from February 26(th). The subjects were therefore divided into two groups depending on the treatment period, namely the pre-seasonal and intra-seasonal groups, December 1(st), 2010 to February 25(th), 2011 and February 26(th) to April 6(th) 2011, respectively. All patients were treated with the new 808 nm diode laser system. A high success rate was achieved in both groups, with no significant difference seen regarding the symptoms of rhinorrhea, obstruction, sneezing, quality of life (QOL) or severity. The 808 nm diode laser offers an excellent solution for the uncomfortable symptoms of allergic rhinitis, and could be equally well applied before or during the Japanese cedar pollen dispersed season.


Integrative Medicine: Acupuncture.
Acupuncture is used to manage pain and a variety of medical and psychological conditions. It modulates nociceptive areas of the brain, affects neuropeptide and purinergic signaling, and stimulates production of opioid neuropeptides. There are many types of acupuncture, including traditional, dry needling, laser, auricular, scalp, Japanese, and Korean. There is evidence that traditional acupuncture is effective in the management of many conditions, with strong evidence of benefit for chronic back pain and osteoarthritis-related knee pain. In the United States, the conditions most commonly managed with acupuncture are low back pain, depression, anxiety, headache, and arthritis. There are no absolute contraindications. Relative contraindications include frailty and febrile illness. Acupuncture should not be used in areas of skin infection or breakdown. Acupuncture typically is avoided during the first trimester of pregnancy. Reports of serious adverse effects are rare but include pneumothorax, infection, organ or tissue injuries, and seizures. Serious adverse effects of electroacupuncture (eg, skin burns, pacemaker or implantable cardioverter-defibrillator dysfunction) are limited to case reports. Thirty-three states in the United States consider acupuncture to be within the scope of practice of physicians. Other states require specific acupuncture training. Medicare provides coverage for acupuncture for management of chronic low back pain.


The association between prehospital care and in-hospital treatment decisions in acute stroke: a cohort study.
Hospital prealerting in acute stroke improves the timeliness of subsequent treatment, but little is known about the impact of prehospital assessments on in-hospital care. Examine the association between prehospital assessments and notification by emergency medical service staff on the subsequent acute stroke care pathway. This was a cohort study of linked patient medical records. Consenting patients with a diagnosis of stroke were recruited from two urban hospitals. Data from patient medical records were extracted and entered into a Cox regression analysis to investigate the association between time to CT request and recording of onset time, stroke recognition (using the Face Arm Speech Test (FAST)) and sending of a prealert message. 151 patients (aged 71±15 years) travelled to hospital via ambulance and were eligible for this analysis. Time of symptom onset was recorded in 61 (40%) cases, the FAST test was positive in 114 (75%) and a prealert message was sent in 65 (44%). Following adjustment for confounding, patients who had time of onset recorded (HR 0.73, 95% CI 0.52 to 1.03), were FAST-positive (HR 0.54, 95% CI 0.37 to 0.80) or were prealerted (HR 0.26, 95% CI 0.18 to 0.38), were more likely to receive a timely CT request in hospital. This study highlights the importance of hospital prealerting, accurate stroke recognition, and recording of onset time. Those not recognised with stroke in a prehospital setting appear to be excluded from the possibility of rapid treatment in hospital, even before they have been seen by a specialist.


Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish.
Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the C/EBPβ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase 3β, which are also essential for stimulating the expression of CEBPβ. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.


Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective.
Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group. WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions. Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired. The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse 'user categories' using a combination of genetics, imaging techniques and neuropsychological assessments.


Esomeprazole alone compared with esomeprazole plus aspirin for the treatment of aspirin-related peptic ulcers.
Aspirin-related peptic ulcers are a common disorder. However, whether or not aspirin should be continued during treatment for aspirin-related ulcers remains unclear. To compare esomeprazole alone with esomeprazole plus aspirin in the treatment of aspirin-related peptic ulcers and to investigate the independent factors associated with the failure of ulcer healing. From January 2008 to July 2011, patients with aspirin-related peptic ulcers were randomized to receive esomeprazole (40 mg per day) alone or esomeprazole (40 mg per day) plus aspirin (100 mg per day) for 8 weeks. The subjects with Helicobacter pylori infection were treated with standard triple therapy. Follow-up endoscopy was carried out at the end of the 8th week. The primary end point was the healing of peptic ulcers. In all, 178 patients (89 receiving esomeprazole alone and 89 receiving esomeprazole plus aspirin) were enrolled and underwent follow-up endoscopy. The healing rate of ulcers by modified intention-to-treat analysis was 82.5% (95% confidence interval (CI), 74.2-90.8%) among patients treated with esomeprazole alone and 81.5% (95% CI, 73.0-90.0%) among patients treated with esomeprazole plus aspirin (difference, 1.0%; 95% CI, -11.2 to 12.6%). The per-protocol analysis yielded similar results (healing rate: 83.1% vs. 83.8%, respectively; difference, 0.7%; 95% CI, -11.2 to 12.6%). Multivariate analysis disclosed that use of steroids during treatment (odds ratio: 5.6; 95% CI, 1.1-27.7%) was the only independent factor associated with the failure of ulcer healing. The observed ulcer healing rates were comparable in the esomeprazole and esomeprazole-plus-aspirin groups, but the wide CIs do not rule out clinically meaningful differences of more than 10%.


Mediators of the relationship between nicotine replacement therapy and smoking abstinence among people living with HIV/AIDS.
Cigarette smoking is highly prevalent among people living with HIV/AIDS and poses unique health risks. Smoking cessation programs tailored to this population have documented improved smoking outcomes with nicotine replacement therapy (NRT). The current study examined 6-month abstinence rates from a randomized clinical trial targeting 412 HIV-positive adult current smokers (51% European American, 19% African American, and 17% Hispanic American) and tested whether psychosocial variables, such as self-efficacy and decisional balance, mediated the relationship between NRT and long-term abstinence. Meeting criteria for complete mediation, 6-month smoking abstinence rates improved significantly with increases in these mediators, and the association of NRT and smoking abstinence was no longer significant once changes in self-efficacy and decisional balance were taken into account . Failure to translate gains in self-efficacy among African Americans into improved abstinence rates accounted for racial/ethnic differences among participants. Specific psychosocial factors, such as self-efficacy, may be particularly amenable to change in cessation interventions and should be addressed with greater awareness of how cultural and social contextual factors impact treatment response among people living with HIV/AIDS.


Improvement of learning and increase in dopamine level in the frontal cortex by methylphenidate in mice lacking dopamine transporter.
The symptoms of attention-deficit/hyperactivity disorder (ADHD) are characterized by inattention and hyperactivity-impulsivity. It is a common childhood neurodevelopmental disorder that often persists into adulthood. Improvements in ADHD symptoms using psychostimulants have been recognized as a paradoxical calming effect. The psychostimulant methylphenidate (MPH) is currently used as the first-line medication for the management of ADHD. Recent studies have drawn attention to altered dopamine-mediated neurotransmission in ADHD, particularly reuptake by the dopamine transporter (DAT). This hypothesis is supported by the observation that DAT knockout mice exhibit marked hyperactivity that is responsive to acute MPH treatment. However, other behaviors relevant to ADHD have not been fully clarified. In the present study, we observed learning impairment in shuttle-box avoidance behavior together with hyperactivity in a novel environment in DAT knockout mice. Methylphenidate normalized these behaviors and enhanced escape activity in the tail suspension test. Interestingly, the effective dose of MPH increased extracellular dopamine in the prefrontal cortex but not striatum, suggesting an important role for changes in prefrontal dopamine in ADHD. Research that uses rodent models such as DAT knockout mice may be useful for elucidating the pathophysiology of ADHD.


Quality control on radiochemical purity in Technetium-99m radiopharmaceuticals labelling: three years of experience on 2280 procedures.
the purpose of this study was to offer an example of evaluations of the ISO9001 certified internal quality assurance (QA) system of 99mTc-radiopharmaceutical preparations and quality control in vivo use, using industrial kits and generators in order to identify possible sources of errors in the procedures labeling and quality control procedures. The study was performed at a single institution over a period of three years (July 1st, 2011 - July 1st, 2014), and included a total of 2280 radiopharmaceutical preparations prepared by four different technologists. All the radiopharmaceutical preparations and quality controls were performed according to each SPC provided by the manufacturer. The radiopharmaceutical preparations were the following (trade names are reported in brackets): 99mTc-albumin colloid [Nanocoll] (n=349), 99mTc-oxidronate [Technescan®hdp] (n=701), 99mTc-exametazime [Ceretec] (n=169), 99mTc-sestamibi [Cardiolite] (n=92), 99mTc-albumin aggregated [Technescan®lyomaa] (n=140), 99mTc-tetrofosmin [Myoview]) (n=567), 99mTc-diethylene triamine pentacetic acid [Technescan®dtpa] (n=254), and 99mTc-dimercapto succinic acid [Renocis®] (n=8). Data were analyzed to determine the number and type of radiopharmaceutical labelling failure and to derive the sources of these failures to define corrective actions and optimize the quality assurance program. A total of 2280 procedures were performed and recorded. Following the quality control procedure six out of the 2280 preparations (0.26%) were non-conforming for clinical use with the RCP limits indicated in the SPC. Five of these were due to gross technical errors in measurements and manual procedures and were immediately repeated, returning within the limits of acceptability. The sixth failure was due to short incubation time, though compliant with the manufacturer's instructions. We concluded that the quality of the final product depends on a controlled production system based on the implementation of specific standard operating procedures (ISO9001, SOP) for each radiopharmaceutical production, according to strict adherence to the SPC of each radiopharmaceutical. Based on these conclusions, in our opinion every quality control suggesting a possible error in the synthesis procedure recommended in the SPC should be immediately reported to the manufacturer, for a revision of the SPC, as well as to the regulatory agencies for an alert. This strategy may in fact allow the continuous improvement of the labelling procedures and therefore the optimization of the quality control procedures frequency to ensure both patients safety and a more rational management of resources for economic sustainability.


Characterization of structural variants with single molecule and hybrid sequencing approaches.
Structural variation is common in human and cancer genomes. High-throughput DNA sequencing has enabled genome-scale surveys of structural variation. However, the short reads produced by these technologies limit the study of complex variants, particularly those involving repetitive regions. Recent 'third-generation' sequencing technologies provide single-molecule templates and longer sequencing reads, but at the cost of higher per-nucleotide error rates. We present MultiBreak-SV, an algorithm to detect structural variants (SVs) from single molecule sequencing data, paired read sequencing data, or a combination of sequencing data from different platforms. We demonstrate that combining low-coverage third-generation data from Pacific Biosciences (PacBio) with high-coverage paired read data is advantageous on simulated chromosomes. We apply MultiBreak-SV to PacBio data from four human fosmids and show that it detects known SVs with high sensitivity and specificity. Finally, we perform a whole-genome analysis on PacBio data from a complete hydatidiform mole cell line and predict 1002 high-probability SVs, over half of which are confirmed by an Illumina-based assembly.


Increasing bioavailability of (R)-alpha-lipoic acid to boost antioxidant activity in the treatment of neuropathic pain.
a-lipoic acid (a-LA) is a potent natural antioxidant because it has a broad spectrum of action towards a great many free radical species and boosts the endogenous antioxidant systems.Although it is a multi-functional molecule, its pharmacokinetic characteristics pose restrictions to its use in the treatment of oxidative stress-dependent illnesses. Formulations that increase the bioavailability of a-LA have a better potential efficacy as adjuvants for the treatment of these conditions.This objective was achieved with a liquid formulation for oral use containing only R-aLA, the natural enantiomeric and most active form of a-lipoic acid.For the first time, the effects of this formulation were evaluated on neuropathic pain, a symptom caused by an increase in oxidative stress, regardless of the underlying cause. Neuropathic patients who have used this dietary supplement noticed an improvement in their quality of life and a significant reduction was observed in a number of certain descriptive pain parameters (intensity, burning, unpleasantness, superficial pain).Undoubtedly further, more in-depth, studies need to be conducted; however, this first investigation confirms the role of R-aLA as an anti-oxidant for the aetiological treatment of peripheral neuropathy. Increasing its plasma bioavailability even after a non-invasive administration through the oral route is a good starting point for proposing a valid adjuvant for the treatment of pain symptoms.


Protein secretion induced by isoproterenol or pentoxifylline in lacrimal gland: Ca2+ effects.
In exorbital lacrimal glands, pentoxifylline (a methylxanthine) induces labeled protein secretion in a dose-related manner: the half-maximal and maximal stimulations are at 4 and 10 mM, respectively. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, labeled protein discharge is strongly stimulated by isoproterenol, via beta-adrenergic receptors: the maximal response is at 10(-6) M. l-Propranolol specifically inhibits the secretory stimulation to isoproterenol in a dose-related manner: for 5 X 10(-6) M isoproterenol in the presence of 10(-5) M papaverine, the half-maximal and maximal inhibitions are at 3 X 10(-7) and 10(-5) M, respectively. The beta-adrenergic response is mimicked by the adenosine 3',5'-cyclic monophosphate (cAMP) analogue dibutyryl cAMP (DBcAMP) at a 10(-3) M concentration. The time course of labeled protein secretion induced by pentoxifylline, DBcAMP, and isoproterenol shows a latency. In the presence or absence of extracellular calcium, pentoxifylline and isoproterenol immediately increase the cAMP intracellular level. Extracellular calcium omission increases the observed latency and also affects the maximal rate of protein secretion. As opposed to the cholinergic agonist, pentoxifylline has only a slight but sustained effect on 45Ca efflux, whereas isoproterenol has none. These data suggest that labeled protein secretion, such as that of peroxidase, can also be stimulated in rat exorbital lacrimal gland, through beta-adrenergic receptors; in the stimulation evoked by a beta-adrenergic agonist, DBcAMP, or methylxanthine, calcium could play a key role.


Enhanced Protein Production in Escherichia coli by Optimization of Cloning Scars at the Vector-Coding Sequence Junction.
Protein production in Escherichia coli is a fundamental activity for a large fraction of academic, pharmaceutical, and industrial research laboratories. Maximum production is usually sought, as this reduces costs and facilitates downstream purification steps. Frustratingly, many coding sequences are poorly expressed even when they are codon-optimized and expressed from vectors with powerful genetic elements. In this study, we show that poor expression can be caused by certain nucleotide sequences (e.g., cloning scars) at the junction between the vector and the coding sequence. Since these sequences lie between the Shine-Dalgarno sequence and the start codon, they are an integral part of the translation initiation region. To identify the most optimal sequences, we devised a simple and inexpensive PCR-based step that generates sequence variants at the vector-coding sequence junction. These sequence variants modulated expression by up to 1000-fold. FACS-seq analyses indicated that low GC content and relaxed mRNA stability (ΔG) in this region were important, but not the only, determinants for high expression.


IDLN-MSP: Idiolocal normalization of real-time methylation-specific PCR for genetic imbalanced DNA specimens.
Sensitive, accurate, and reliable measurements of tumor cell-specific DNA methylation changes are of fundamental importance in cancer diagnosis, prognosis, and monitoring. Real-time methylation-specific PCR (MSP) using intercalating dyes is an established method of choice for this purpose. Here we present a simple but crucial adaptation of this widely applied method that overcomes a major obstacle: genetic abnormalities in the DNA samples, such as aneuploidy or copy number variations, that could result in inaccurate results due to improper normalization if the copy numbers of the target and reference sequences are not the same. In our idiolocal normalization (IDLN) method, the locus for the normalizing, methylation-independent reference amplification is chosen close to the locus of the methylation-dependent target amplification. This ensures that the copy numbers of both the target and reference sequences will be identical in most cases if they are close enough to each other, resulting in accurate normalization and reliable comparative measurements of DNA methylation in clinical samples when using real-time MSP.


The changing spectrum of Saccharomycotina yeasts causing candidemia: phylogeny mirrors antifungal susceptibility patterns for azole drugs and amphothericin B.
Ascomycetous yeast species belonging to the subphylum Saccharomycotina (Ascomycota, Fungi) may cause a variety of pathologies in humans. Candida albicans accounts for almost half of candidemia cases but the emergence of uncommon yeasts in the clinical setting is increasing. Here, we highlight the epidemiology of Saccharomycotina budding yeasts causing bloodstream infections, address antifungal susceptibility patterns and unravel how the latter corresponds to their phylogenetic relationship. Only studies applying Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and/or sequence-based identification methods were considered. A ribosomal DNA-based phylogeny was used to present phylogenetic relationships of yeasts pathogens and their close relatives and to show how the antifungal susceptibility patterns for amphotericin B and azole drugs correlate with the clades found. Candida albicans was still the leading cause of yeast-related sepsis, but 22 other Saccharomycotina yeast species were also identified as a common cause of sepsis based on the literature. Similar minimum inhibitory concentration (MIC) values are found between phylogenetically closely related species and appear to be clade-specific to a large extent. This demonstrates that phylogeny may serve as a first guidance for treatment of emerging yeasts with uncommon susceptibility patterns due to intrinsic resistance.


A 15N-poor isotopic composition for the solar system as shown by Genesis solar wind samples.
The Genesis mission sampled solar wind ions to document the elemental and isotopic compositions of the Sun and, by inference, of the protosolar nebula. Nitrogen was a key target element because the extent and origin of its isotopic variations in solar system materials remain unknown. Isotopic analysis of a Genesis Solar Wind Concentrator target material shows that implanted solar wind nitrogen has a (15)N/(14)N ratio of 2.18 ± 0.02 × 10(-3) (that is, ≈40% poorer in (15)N relative to terrestrial atmosphere). The (15)N/(14)N ratio of the protosolar nebula was 2.27 ± 0.03 × 10(-3), which is the lowest (15)N/(14)N ratio known for solar system objects. This result demonstrates the extreme nitrogen isotopic heterogeneity of the nascent solar system and accounts for the (15)N-depleted components observed in solar system reservoirs.


Image deblurring and super-resolution by adaptive sparse domain selection and adaptive regularization.
As a powerful statistical image modeling technique, sparse representation has been successfully used in various image restoration applications. The success of sparse representation owes to the development of the l(1)-norm optimization techniques and the fact that natural images are intrinsically sparse in some domains. The image restoration quality largely depends on whether the employed sparse domain can represent well the underlying image. Considering that the contents can vary significantly across different images or different patches in a single image, we propose to learn various sets of bases from a precollected dataset of example image patches, and then, for a given patch to be processed, one set of bases are adaptively selected to characterize the local sparse domain. We further introduce two adaptive regularization terms into the sparse representation framework. First, a set of autoregressive (AR) models are learned from the dataset of example image patches. The best fitted AR models to a given patch are adaptively selected to regularize the image local structures. Second, the image nonlocal self-similarity is introduced as another regularization term. In addition, the sparsity regularization parameter is adaptively estimated for better image restoration performance. Extensive experiments on image deblurring and super-resolution validate that by using adaptive sparse domain selection and adaptive regularization, the proposed method achieves much better results than many state-of-the-art algorithms in terms of both PSNR and visual perception.


Genomic Serotyping, Clinical Manifestations, and Antimicrobial Resistance of Nontyphoidal Salmonella Gastroenteritis in Hospitalized Children in Ho Chi Minh City, Vietnam.
Nontyphoidal Salmonella (NTS) are among the most common etiological agents of diarrheal diseases worldwide and have become the most commonly detected bacterial pathogen in children hospitalized with diarrhea in Vietnam. Aiming to better understand the epidemiology, serovar distribution, antimicrobial resistance (AMR), and clinical manifestation of NTS gastroenteritis in Vietnam, we conducted a clinical genomics investigation of NTS isolated from diarrheal children admitted to one of three tertiary hospitals in Ho Chi Minh City. Between May 2014 and April 2016, 3,166 children hospitalized with dysentery were recruited into the study; 478 (∼15%) children were found to be infected with NTS by stool culture. Molecular serotyping of the 450 generated genomes identified a diverse collection of serogroups (B, C1, C2 to C3, D1, E1, G, I, K, N, O, and Q); however, Salmonella enterica serovar Typhimurium was the most predominant serovar, accounting for 41.8% (188/450) of NTS isolates. We observed a high prevalence of AMR to first-line treatments recommended by WHO, and more than half (53.8%; 242/450) of NTS isolates were multidrug resistant (MDR; resistant to ≥3 antimicrobial classes). AMR gene detection positively correlated with phenotypic AMR testing, and resistance to empirical antimicrobials was associated with a significantly longer hospitalization (0.91 days; P = 0.04). Our work shows that genome sequencing is a powerful epidemiological tool to characterize the serovar diversity and AMR profiles in NTS. We propose a revaluation of empirical antimicrobials for dysenteric diarrhea and endorse the use of whole-genome sequencing for sustained surveillance of NTS internationally.


Potential Roles for Probiotics in the Treatment of COVID-19 Patients and Prevention of Complications Associated with Increased Antibiotic Use.
Medical care for patients hospitalized with COVID-19 is an evolving process. Most COVID-19 inpatients (58-95%) received empiric antibiotics to prevent the increased mortality due to ventilator-associated pneumonia and other secondary infections observed in COVID-19 patients. The expected consequences of increased antibiotic use include antibiotic-associated diarrhea (AAD) and Clostridioides difficile infections (CDI). We reviewed the literature (January 2020-March 2021) to explore strategies to reduce these consequences. Antimicrobial stewardship programs were effective in controlling antibiotic use during past influenza epidemics and have also been shown to reduce healthcare-associated rates of CDI. Another potential strategy is the use of specific strains of probiotics shown to be effective for the prevention of AAD and CDI prior to the pandemic. During 2020, there was a paucity of published trials using these two strategies in COVID-19 patients, but trials are currently ongoing. A multi-strain probiotic mixture was found to be effective in reducing COVID-19-associated diarrhea in one trial. These strategies are promising but need further evidence from trials in COVID-19 patients.


Sex Differences in Clinical and Functional Outcomes among Patients Treated in an Early Intervention Service for Psychotic Disorders: An Observational Study.
It has been shown that men with a longstanding psychotic disorder have worse clinical and functional outcomes than women. Our objectives were to examine whether these sex differences are also present among patients treated in an early intervention service (EIS) for psychosis and to determine if these differences are related to risk factors other than sex. Patients (N = 569) were assessed for demographic/clinical characteristics at entry and for symptoms/functioning over 2 years of treatment. Clinical outcomes included remission of positive, negative, and total symptoms. Functional outcomes included good functioning and functional remission. Logistic regression models examined the relationship between sex and outcomes after 1 and 2 years of treatment while controlling for the influence of other risk factors. Men reported to be less educated and have a longer duration of untreated psychosis, poorer childhood and early adolescent premorbid functioning, higher rates of substance abuse/dependence disorders, greater severity of baseline negative symptoms, and poorer baseline social/occupational functioning than women. Women were more likely to achieve symptom remission than men after 2 years of treatment (negative odds ratio [OR], 1.69; 95% confidence interval [CI], 1.02 to 2.78; total OR, 1.79; 95% CI, 1.08 to 2.98). Women were also more likely than men to exhibit good functioning (OR, 1.61; 95% CI, 1.04 to 2.49) after 1 but not after 2 years of treatment. These results did not persist after controlling for other risk factors that could confound these associations (i.e., childhood premorbid functioning and age at onset of psychosis). Sex differences seen in outcomes among patients treated in an EIS for psychosis may be largely influenced by the disparity of other risk factors that exist between the 2 sexes.


Nucleoside triphosphate binding to DNA polymerase III holoenzyme of Escherichia coli. A direct photoaffinity labeling study.
The physical basis of ATP binding and activation of DNA polymerase III holoenzyme was studied by an ultraviolet irradiation cross-linking technique. ATP and dATP were photocrosslinked to the alpha, tau, gamma, and delta subunits of holoenzyme; photocrosslinking of dATP was competitively inhibited by ATP. No photocrosslinking was observed with GTP or CTP, nor did GTP, CTP, or UTP inhibit cross-linking of ATP. ADP and adenosine 5'-O-(3-thio)-triphosphate, both potent inhibitors of ATP activation of holoenzyme, inhibited cross-linking of ATP to tau, gamma, and delta subunits, but not to the alpha subunit, suggesting that one or more of these subunits are ATP (or dATP)-binding sites. Photocrosslinking of dTTP to the ATP-activated holoenzyme was exclusively to the epsilon subunit, the dnaQ ( mutD ) gene product; dCTP and dGTP were not photocrosslinked to any subunit. Binding of dTTP was enhanced by ATP, but by no other nucleotide (or deoxynucleotide). This binding of dTTP to epsilon, a subunit likely responsible for regulation of proofreading by the holoenzyme, may function in the control of the fidelity of replication.


A systematic review and meta-analysis of caudal block as compared to noncaudal regional techniques for inguinal surgeries in children.
This systematic review and meta-analysis were designed to compare the analgesic effectiveness and adverse effects with the use of caudal analgesia as compared to noncaudal regional analgesia techniques in children undergoing inguinal surgeries. MEDLINE, EMBASE, and CENTRAL (Cochrane) databases were searched for randomized control trials published in English language from 1946 up to 2013. Use of rescue analgesia and adverse effects were considered as primary and secondary outcomes, respectively. Outcomes were pooled using random effects model and reported as risk ratio (RR) with 95% CI. Out of 3240 hits and 24 reports for final selection, 17 were included in this review. Caudal analgesia was found to be better in both early (RR = 0.81 [0.66, 0.99], P = 0.04) and late (RR = 0.81 [0.69, 0.96], P = 0.01) periods, but with a significant risk of motor block and urinary retention. According to GRADE, the quality of evidence was moderate. Although potentially superior, caudal analgesia increases the chance of motor block and urinary retention. There are limited studies to demonstrate that the technical superiority using ultrasound translates into better clinical success with the inguinal nerve blocks.


Paracrine upregulation of VEGF receptor mRNA in endothelial cells by hypoxia-exposed hep G2 cells.
Although vascular endothelial growth factor (VEGF) plays a role in the growth of hypervascular tumors, mechanisms for paracrine regulation of its receptor expression on vascular endothelial cells remain unknown. This study aimed to investigate whether VEGF released from hypoxia-exposed Hep G2 cells alters expression of the two distinct receptors, kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase 1 (flt-1), in human umbilical venous endothelial cells (HUVEC). Hep G2 cells were cultured in 20% or 1% O2 for 16 h to examine induction of VEGF mRNA and its protein expression. Conditioned medium from Hep G2 cells (CM) was applied to HUVEC under normoxic conditions, and expression of mRNA for the VEGF receptors was determined by RT-PCR. In response to the hypoxic challenge, Hep G2 cells upregulated VEGF mRNA and the release of VEGF. Hypoxia-CM preferentially stimulated the mRNA expression of flt-1 but not that of KDR in HUVEC. When the VEGF release from hypoxia-exposed Hep G2 cells was blocked by its antisense oligodeoxynucleotide, the endothelial flt-1 mRNA upregulation elicited by the hypoxia-CM was still maintained. These results suggest that hypoxia-exposed Hep G2 cells not only produce VEGF but also evolve paracrine induction of flt-1 through VEGF-independent mechanisms.


Religious involvement, suicidal ideation and behavior in mainland China.
Little is known about relations between religious involvement and suicidal behaviors in mainland China. This study aims to examine the association between religious involvement and suicidal ideation, planning, and attempts within a general community population controlling for socio-demographic, physical, and mental health factors. Data were examined from a population-based sample of 2,769 community-dwelling adults in the province of Ningxia China, where nearly 40% are Muslim, 11% other religious affiliations, and 49% no religion. Four separate logistic regression models examined correlations between religious involvement and self-reported suicidal thoughts, plans, and attempts. Analyses were also stratified by Muslim affiliation (n = 1103) and no religion (n = 1,366). Bivariate analyses in the overall sample demonstrated that higher personal religiosity scores (χ(2) = 6.8, p < 0.01) and total religiosity scores (χ(2) = 5.1, p < 0.05) were positively correlated with developing a suicidal plan, which disappeared after controlling for demographic characteristics. Otherwise, no significant correlations were found between any religious characteristic and suicidal ideation, plan, or attempt in either Muslims or those with no religion. In contrast to most previous studies, religious involvement plays less of a role in suicidal behaviors in at least one province of mainland China.


Viking first encounter of phobos: preliminary results.
During the last 2 weeks of February 1977, an intensive scientific investigation of the martian satellite Phobos was conducted by the Viking Orbiter-1 (VO-1) spacecraft. More than 125 television pictures were obtained during this period and infrared observations were made. About 80 percent of the illuminated hemisphere was imaged at a resolution of about 30 meters. Higher resolution images of limited areas were also obtained. Flyby distances within 80 kilometers of the surface were achieved. An estimate of the mass of Phobos (GM) was obtained by observing the effect of Phobos's gravity on the orbit of VO-1 as sensed by Earth-based radiometric tracking. Preliminary results indicate a value of GM of 0.00066 +/- 0.00012 cubic kilometer per second squared (standard deviation of 3) and a mean density of about 1.9 +/- 0.6 gram per cubic centimeter (standard deviation of 3). This low density, together with the low albedo and the recently determined spectral reflectance, suggest that Phobos is compositionally similar to type I carbonaceous chondrites. Thus, either this object formed in the outer part of the asteroid belt or Lewis's theory that such material cannot condense at 1.5 astronomical units is incorrect. The data on Phobos obtained during this first encounter period are comparable in quantity to all of the data on Mars returned by Mariner flights 4, 6, and 7.


Applying heuristic inquiry to nurse migration from the UK to Australia.
Background Heuristic inquiry is a research approach that improves understanding of the essence of an experience. This qualitative method relies on researchers' ability to discover and interpret their own experience while exploring those of others. Aim To present a discussion of heuristic inquiry's methodology and its application to the experience of nurse migration. Discussion The researcher's commitment to the research is central to heuristic inquiry. It is immersive, reflective, reiterative and a personally-affecting method of gathering knowledge. Researchers are acknowledged as the only people who can validate the findings of the research by exploring their own experiences while also examining those of others with the same experiences to truly understand the phenomena being researched. This paper presents the ways in which the heuristic process guides this discovery in relation to traditional research steps. Conclusion Heuristic inquiry is an appropriate method for exploring nurses' experiences of migration because nurse researchers can tell their own stories and it brings understanding of themselves and the phenomenon as experienced by others. Implications for practice Although not a popular method in nursing research, heuristic inquiry offers a depth of exploration and understanding that may not be revealed by other methods.


The impact of deep sternal wound infection on long-term survival after coronary artery bypass grafting.
To identify the impact of deep sternal wound infection (DSWI) on long-term survival after coronary artery bypass grafting (CABG). DSWI following CABG is an infrequent, yet devastating complication with increased morbidity and mortality. However, little has been published regarding the impact of DSWI on long-term mortality. We studied 3,760 consecutive patients who underwent isolated CABG between 1992 and 2002. Patients with CABG and no DSWI were compared with those in whom DSWI developed. Long-term survival data (mean follow-up, 5.2 years) were obtained from the National Death Index. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for DSWI was determined by logistic regression analysis, and each patient with DSWI was then matched to 10 patients without DSWI. DSWI developed in 40 of 3,760 patients (1.1%). Independent predictors for DSWI were diabetes (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.7 to 11.6; p < 0.001), hemodynamic instability preoperatively (OR, 4.0; 95% CI, 1.2 to 13.9; p = 0.026), preoperative renal failure on dialysis (OR, 3.4; 95% CI, 1.0 to 13.6; p = 0.049), use of bilateral internal thoracic arteries (OR, 2.6; 95% CI, 1.3 to 5.3; p = 0.010), and sepsis and/or endocarditis after CABG (OR, 29.9; 95% CI, 11.7 to 76.4; p < 0.001). Patients with DSWI had prolonged length of stay (35.0 days vs 16.4 days; p < 0.001); however, there was no difference in early mortality between matched groups. After adjustment for preoperative, intraoperative, and postoperative factors, the adjusted hazard ratio of long-term mortality for patients with DSWI was 2.44 (95% CI, 1.51 to 3.92; p < 0.001). Patients without DSWI had a better 5-year survival rate (72.8 +/- 2.4% vs 50.8.6 +/- 8.5% [mean +/- SE]; p = 0.0007 between matched groups). We found that DSWI following CABG was associated with increased long-term mortality during a 10-year follow-up study.


Serum vitamin B12 levels in patients with primary hepatocellular carcinoma during treatment with CB3717.
Elevated Serum B12 levels were found at diagnosis in five of eleven patients with primary hepatocellular carcinoma. During chemotherapy either with CB3717 or VP16 the serum B12 rose dramatically, in one case reaching levels ten times the upper limit of normal. However, the serum LD activities did not change in parallel with the serum B12 levels suggesting that there was little necrosis of the tumour or the liver. With two out of five patients with other types of cancer the serum B12 levels also increased but less markedly. This data seems to suggest that the serum B12 level may not be as good a tumour marker for hepatocellular carcinoma as has been suggested and indeed may be influenced by the chemotherapeutic agent.


Predictive Value of an Age-Based Modification of the National Early Warning System in Hospitalized Patients With COVID-19.
Early recognition of high-risk patients with coronavirus disease 2019 (COVID-19) may improve outcomes. Although many predictive scoring systems exist, their complexity may limit utility in COVID-19. We assessed the prognostic performance of the National Early Warning Score (NEWS) and an age-based modification (NEWS+age) among hospitalized COVID-19 patients enrolled in a prospective, multicenter US Military Health System (MHS) observational cohort study. Hospitalized adults with confirmed COVID-19 not requiring invasive mechanical ventilation at admission and with a baseline NEWS were included. We analyzed each scoring system's ability to predict key clinical outcomes, including progression to invasive ventilation or death, stratified by baseline severity (low [0-3], medium [4-6], and high [≥7]). Among 184 included participants, those with low baseline NEWS had significantly shorter hospitalizations (P < .01) and lower maximum illness severity (P < .001). Most (80.2%) of low NEWS vs 15.8% of high NEWS participants required no or at most low-flow oxygen supplementation. Low NEWS (≤3) had a negative predictive value of 97.2% for progression to invasive ventilation or death; a high NEWS (≥7) had high specificity (93.1%) but low positive predictive value (42.1%) for such progression. NEWS+age performed similarly to NEWS at predicting invasive ventilation or death (NEWS+age: area under the receiver operating characteristics curve [AUROC], 0.69; 95% CI, 0.65-0.73; NEWS: AUROC, 0.70; 95% CI, 0.66-0.75). NEWS and NEWS+age showed similar test characteristics in an MHS COVID-19 cohort. Notably, low baseline scores had an excellent negative predictive value. Given their easy applicability, these scoring systems may be useful in resource-limited settings to identify COVID-19 patients who are unlikely to progress to critical illness.


Exxon Valdez to Deepwater Horizon: comparable toxicity of both crude oils to fish early life stages.
The 2010 Deepwater Horizon disaster in the Gulf of Mexico was the largest oil spill in United States history. Crude oils are highly toxic to developing fish embryos, and many pelagic fish species were spawning in the northern Gulf in the months before containment of the damaged Mississippi Canyon 252 (MC252) wellhead (April-July). The largest prior U.S. spill was the 1989 grounding of the Exxon Valdez that released 11 million gallons of Alaska North Slope crude oil (ANSCO) into Prince William Sound. Numerous studies in the aftermath of the Exxon Valdez spill defined a conventional crude oil injury phenotype in fish early life stages, mediated primarily by toxicity to the developing heart. To determine whether this type of injury extends to fishes exposed to crude oil from the Deepwater Horizon - MC252 incident, we used zebrafish to compare the embryotoxicity of ANSCO alongside unweathered and weathered MC252 oil. We also developed a standardized protocol for generating dispersed oil water-accommodated fractions containing microdroplets of crude oil in the size range of those detected in subsurface plumes in the Gulf. We show here that MC252 oil and ANSCO cause similar cardiotoxicity and photo-induced toxicity in zebrafish embryos. Morphological defects and patterns of cytochrome P450 induction were largely indistinguishable and generally correlated with polycyclic aromatic compound (PAC) composition of each oil type. Analyses of embryos exposed during different developmental windows provided additional insight into mechanisms of crude oil cardiotoxicity. These findings indicate that the impacts of MC252 crude oil on fish embryos and larvae are consistent with the canonical ANSCO cardiac injury phenotype. For those marine fish species that spawned in the northern Gulf of Mexico during and after the Deepwater Horizon incident, the established literature can therefore inform the assessment of natural resource injury in the form of potential year-class losses.


Thermal denaturation of hydrated wool keratin by 1H solid-state NMR.
Thermal denaturation of hydrated keratin in wool was investigated by NMR using 1H wide-line spectra to obtain the phase composition and 1H spin-diffusion experiments using a double-quantum filter to obtain the domain sizes for the wool fibers. The denaturation process detected by DSC takes place for wool fibers in deuterated water in the temperature range 140-144 degreeC. The phase composition measured by 1H wide line NMR spectra reveals a rigid, semirigid and an amorphous phase for temperatures in the range 25-160 degreeC. A dramatic change in the phase composition was detected around 142 degreeC, corresponding to the denaturation temperature. The morphological domain sizes measured by 1H spin-diffusion NMR experiments were obtain from the solutions of the spin-diffusion equations for two-dimensional rectangular and cylindrical morphologies. The keratin mobility gradient in the interfacial region at different denaturation temperatures was measured from the 1H spin-diffusion data. A qualitative model describing the denaturation process of hydrated keratin protein was developed that explains the changes in domain thickness, spin diffusivities, phase composition, and thermodynamic parameters.


Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance.
Insulin resistance contributes to a number of metabolic disorders, including type II diabetes, hypertension, and atherosclerosis. Cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth hormone, are known to cause insulin resistance, but the mechanisms by which they inhibit the cellular response to insulin have not been elucidated. One mechanism by which these agents could cause insulin resistance is by inducing the expression of cellular proteins that inhibit insulin receptor (IR) signaling. Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling pathways, the expression of which is regulated by certain cytokines. SOCS proteins are therefore attractive candidates as mediators of cytokine-induced insulin resistance. We have found that SOCS-1 and SOCS-6 interact with the IR when expressed in human hepatoma cells (HepG2) or in rat hepatoma cells overexpressing the human IR. In SOCS-1-expressing cells, insulin treatment increases the extent of interaction with the IR, whereas in SOCS-6-expressing cells the association with the IR appears to require insulin treatment. SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro. These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes.


The use of mycobacterial interspersed repetitive unit typing and whole genome sequencing to inform tuberculosis prevention and control activities.
Molecular strain typing of Mycobacterium tuberculosis has been possible for only about 20 years; it has significantly improved our understanding of the evolution and epidemiology of Mycobacterium tuberculosis and tuberculosis disease. Mycobacterial interspersed repetitive unit typing, based on 24 variable number tandem repeat unit loci, is highly discriminatory, relatively easy to perform and interpret and is currently the most widely used molecular typing system for tuberculosis surveillance. Nevertheless, clusters identified by mycobacterial interspersed repetitive unit typing sometimes cannot be confirmed or adequately defined by contact tracing and additional methods are needed. Recently, whole genome sequencing has been used to identify single nucleotide polymorphisms and other mutations, between genotypically indistinguishable isolates from the same cluster, to more accurately trace transmission pathways. Rapidly increasing speed and quality and reduced costs will soon make large scale whole genome sequencing feasible, combined with the use of sophisticated bioinformatics tools, for epidemiological surveillance of tuberculosis.


Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus Mesenchymal-Like Prostate Cancer Cells.
HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaP(E) and ARCaP(M) cells in an EMT model. Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or prostate stroma cells. Prostate (Pt-N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to radiation treatment in ARCaP(E) cells compared to ARCaP(M) cells. However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells. Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin and integrin alpha v in cancer cells induce cell survival signals and mediate resistance to cancer treatments such as radiation.


The role of uterine artery Doppler in predicting adverse pregnancy outcome.
The complications of placental insufficiency, pre-eclampsia and fetal growth restriction (FGR) are major causes of perinatal as well as maternal morbidity and mortality. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, and histopathological studies suggest that this is due to trophoblastic invasion of the spiral arteries and their conversion into low-resistance vessels. Failure of trophoblastic invasion is associated with complications of uteroplacental insufficiency. Several Doppler screening studies, both in the second and more recently in the first trimester of pregnancy, have demonstrated an association between increased impedance to flow in the uterine arteries and subsequent development of pre-eclampsia, FGR and perinatal death.


Decision tools in health care: focus on the problem, not the solution.
Systematic reviews or randomised-controlled trials usually help to establish the effectiveness of drugs and other health technologies, but are rarely sufficient by themselves to ensure actual clinical use of the technology. The process from innovation to routine clinical use is complex. Numerous computerised decision support systems (DSS) have been developed, but many fail to be taken up into actual use. Some developers construct technologically advanced systems with little relevance to the real world. Others did not determine whether a clinical need exists. With NHS investing 5 billion pounds sterling in computer systems, also occurring in other countries, there is an urgent need to shift from a technology-driven approach to one that identifies and employs the most cost-effective method to manage knowledge, regardless of the technology. The generic term, 'decision tool' (DT), is therefore suggested to demonstrate that these aids, which seem different technically, are conceptually the same from a clinical viewpoint. Many computerised DSSs failed for various reasons, for example, they were not based on best available knowledge; there was insufficient emphasis on their need for high quality clinical data; their development was technology-led; or evaluation methods were misapplied. We argue that DSSs and other computer-based, paper-based and even mechanical decision aids are members of a wider family of decision tools. A DT is an active knowledge resource that uses patient data to generate case specific advice, which supports decision making about individual patients by health professionals, the patients themselves or others concerned about them. The identification of DTs as a consistent and important category of health technology should encourage the sharing of lessons between DT developers and users and reduce the frequency of decision tool projects focusing only on technology. The focus of evaluation should become more clinical, with the impact of computer-based DTs being evaluated against other computer, paper- or mechanical tools, to identify the most cost effective tool for each clinical problem. We suggested the generic term 'decision tool' to demonstrate that decision-making aids, such as computerised DSSs, paper algorithms, and reminders are conceptually the same, so the methods to evaluate them should be the same.


CO₂ enrichment can produce high red leaf lettuce yield while increasing most flavonoid glycoside and some caffeic acid derivative concentrations.
Carbon dioxide (CO2) enrichment is a common practice in greenhouses to increase crop yields up to 30%. Yet, reports on the effect on foliar phenolic compounds vary. We studied the effect on two red leaf lettuce cultivars, grown for 25 days in growth chambers at CO2 concentrations of 200 or 1,000 ppm, with some plants exchanged between treatments after 11 days. As expected, head mass increased with higher CO2 concentration. Regression analysis, corrected for head mass, showed increased concentrations of most flavonoid glycosides at high CO2 concentrations while only some caffeic acid derivatives were increased, and not uniformly in both cultivars. Sugar concentrations increased with CO2 concentration. Generally, conditions in the 10 days before harvest determined concentrations. We suspect that phenolic compounds were mainly accumulated because plenty of precursors were available. The results indicate that CO2 enrichment can result in high yields of red leaf lettuce rich in phenolic compounds.


[Executive function deficits in normal aging, Alzheimer's disease, and frontotemporal dementia].
An increasing number of studies suggest that executive functions are among the first cognitive functions to bear negative effects of normal aging. Executive functions also appear to be early affected in Alzheimer's disease and frontotemporal dementia. This article reviews studies in neuropsychology and experimental cognitive psychology with a focus on normal aging, Alzheimer's disease as well as frontotemporal dementia. Study results suggest that so called executive tasks are not equally impaired by normal ageing or dementia in agreement with the recent theoretical models, which state that a set of distinct elementary mechanisms subserve the executive control of cognitive behavior. These models are therefore particularly relevant to address issues stemming from aging.


Fast MRI evaluation of pulmonary progressive massive fibrosis with VIBE and HASTE sequences: comparison with CT.
The aim of this prospective study was to evaluate the diagnostic utility of volumetric interpolated breath-hold examination (VIBE) and half-Fourier-acquisition single-shot turbo spin-echo (HASTE) fast magnetic resonance imaging (MRI) sequences in the evaluation of pulmonary progressive massive fibrosis (PMF) in comparison with computed tomography (CT) imaging. If fast MRI is proven to be diagnostically significant, this modality can be used for diagnosis and follow-up studies of PMF patients. Twenty-two PMF lesions from 20 coal workers were evaluated. After CT imaging, patients underwent pre-contrast VIBE, contrast-enhanced VIBE, and HASTE MRI studies for detection and evaluation of the PMF lesions. Measurements of the three groups were evaluated with intra-class coefficients. Correlation levels between sizes, image quality, and artifact were evaluated with linear Pearson correlation analysis. There was almost perfect agreement among radiologists for lesion detection with kappa analysis. There was significant agreement between three MRI study groups and gold standard CT images. We found the best agreement values with contrast- enhanced VIBE images for lesion detection and image quality in comparison with CT imaging. Presence of artifact was also lowest with this protocol. With fast MRI sequences in pulmonary imaging, image quality has significantly improved being very close to that of CT studies. In this study, contrast-enhanced VIBE protocol provided the best depiction of PMF lesions. This protocol may be an alternative choice for CT, avoiding the use of iodinated contrast material and minimizing exposure to ionizing radiation for follow-up studies.


Long-term global and regional brain volume changes following severe traumatic brain injury: a longitudinal study with clinical correlates.
Traumatic brain injury (TBI) results in neurodegenerative changes that progress for months, perhaps even years post-injury. However, there is little information on the spatial distribution and the clinical significance of this late atrophy. In 24 patients who had sustained severe TBI we acquired 3D T1-weighted MRIs about 8 weeks and 12 months post-injury. For comparison, 14 healthy controls with similar distribution of age, gender and education were scanned with a similar time interval. For each subject, longitudinal atrophy was estimated using SIENA, and atrophy occurring before the first scan time point using SIENAX. Regional distribution of atrophy was evaluated using tensor-based morphometry (TBM). At the first scan time point, brain parenchymal volume was reduced by mean 8.4% in patients as compared to controls. During the scan interval, patients exhibited continued atrophy with percent brain volume change (%BVC) ranging between -0.6% and -9.4% (mean -4.0%). %BVC correlated significantly with injury severity, functional status at both scans, and with 1-year outcome. Moreover, %BVC improved prediction of long-term functional status over and above what could be predicted using functional status at approximately 8 weeks. In patients as compared to controls, TBM (permutation test, FDR 0.05) revealed a large coherent cluster of significant atrophy in the brain stem and cerebellar peduncles extending bilaterally through the thalamus, internal and external capsules, putamen, inferior and superior longitudinal fasciculus, corpus callosum and corona radiata. This indicates that the long-term atrophy is attributable to consequences of traumatic axonal injury. Despite progressive atrophy, remarkable clinical improvement occurred in most patients.


Effects of visual span on reading speed and parafoveal processing in eye movements during sentence reading.
The visual span (or ''uncrowded window''), which limits the sensory information on each fixation, has been shown to determine reading speed in tasks involving rapid serial visual presentation of single words. The present study investigated whether this is also true for fixation durations during sentence reading when all words are presented at the same time and parafoveal preview of words prior to fixation typically reduces later word-recognition times. If so, a larger visual span may allow more efficient parafoveal processing and thus faster reading. In order to test this hypothesis, visual span profiles (VSPs) were collected from 60 participants and related to data from an eye-tracking reading experiment. The results confirmed a positive relationship between the readers' VSPs and fixation-based reading speed. However, this relationship was not determined by parafoveal processing. There was no evidence that individual differences in VSPs predicted differences in parafoveal preview benefit. Nevertheless, preview benefit correlated with reading speed, suggesting an independent effect on oculomotor control during reading. In summary, the present results indicate a more complex relationship between the visual span, parafoveal processing, and reading speed than initially assumed.


Effect of guided self-determination youth intervention integrated into outpatient visits versus treatment as usual on glycemic control and life skills: a randomized clinical trial in adolescents with type 1 diabetes.
Providing care for adolescents with type 1 diabetes is complex, demanding, and often unsuccessful. Guided self-determination (GSD) is a life skills approach that has been proven effective in caring for adults with type 1 diabetes. To improve care, GSD was revised for adolescents, their parents, and interdisciplinary healthcare providers (HCP) to create GSD-Youth (GSD-Y). We evaluated the impact of GSD-Y after it was integrated into pediatric outpatient visits versus treatment-as-usual, focusing on glycemic control and the development of life skills in adolescents with type 1 diabetes. Seventy-one adolescents (mean age: 15 years, mean duration of diabetes: 5.7 years, mean HbA1c: 77 mmol/mol (9.1%), upon entering the study) from two pediatric departments were randomized into a GSD-Y group (n = 37, GSD-Y was provided during individual outpatient sessions) versus a treatment-as-usual group (n = 34). The primary outcome was the HbA1c measurement. The secondary outcomes were life skills development (assessed by self-reported psychometric scales), self-monitored blood glucose levels, and hypo- and hyperglycemic episodes. The analysis followed an intention-to-treat basis. Fifty-seven adolescents (80%) completed the trial, and 53 (75%) completed a six-month post-treatment follow-up. No significant effect of GSD-Y on the HbA1c could be detected in a mixed-model analysis after adjusting for the baseline HbA1c levels and the identity of the HCP (P = 0.85). GSD-Y significantly reduced the amotivation for diabetes self-management after adjusting for the baseline value (P = 0.001). Compared with the control group, the trial completion was prolonged in the GSD-Y group (P <0.001), requiring more visits (P = 0.05) with a higher rate of non-attendance (P = 0.01). GSD-Y parents participated in fewer of the adolescents' visits (P = 0.05) compared with control parents. Compared with treatment-as-usual, GSD-Y did not improve HbA1c levels, but it did decrease adolescents' amotivation for diabetes self-management. ISRCTN 54243636, registered on 10 January 2010. Life skills for adolescents with type 1 diabetes and their parents.


Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10.
Several subsets of innate immune cells, all with unique properties, reside within the intestinal lamina propria. However, compared with intestinal dendritic cells (DCs), intestinal macrophages are less well characterized. In this study, we examined the properties of macrophages in the colonic lamina propria (LMφ). Colonic DCs (LDC) showed LPS-induced production of IL-12p40. In contrast, LMφ showed constitutive IL-10 production and unresponsiveness to LPS in terms of inflammatory cytokine production. Comparison of the gene expression profiles between LMφ and LDC revealed that LMφ preferentially expressed IL-10-related genes. LMφ obtained from mice lacking IL-10 or Stat3 showed hyperproduction of tumour necrosis factor (TNF)-α and IL-6 in response to LPS. IL-10 production in the large intestine was mainly induced by LMφ and regulatory T cells and was dependent on the presence of commensal microbiota. Accordingly, LMφ from germ-free mice showed less production of IL-10 and increased levels of LPS-induced TNF-α and IL-6 production. Taken together, these results demonstrate that the activity of LMφ to produce pro-inflammatory cytokines is negatively regulated through commensal microbiota-dependent IL-10 production in the large intestine.


Mental health services, care provision, and professional support for people diagnosed with borderline personality disorder: systematic review of service-user, family, and carer perspectives.
Mental health professionals' attitudes to people with Borderline Personality Disorder can be negative. No systematic review to date has examined how service-users and their families experience professional care. To critically synthesise evidence of service-users' and families' subjective experience of mental health care for borderline personality disorder. Multiple computerised databases were searched using comprehensive terms. All relevant, English language empirical studies were included. We read and critically assessed all papers independently. Study findings were subject to a meta-synthesis. A total of 38 studies were included. Analysis revealed four themes for service-users: assessment and diagnosis; approach of professionals; therapeutic interventions, and service provision; two broad themes for family/carers: support, burden, and information; and experience of professional and therapeutic approaches. Both groups expected to receive professional healthcare, and were clear they valued professionalism, respect, compassion and the therapeutic nature of positive relationships with professionals. Expectations were jeopardised where difficulties with knowledge, communication, information sharing, and support were perceived. Service-users and families/carers should expect to receive high quality, fair and equal care. In light of current evidence, a cultural shift towards more relational, person centred and recovery-focused care could improve experiences.