Alpha-interferon treatment in hepatitis B.
Pegylated interferon-α (PEG-IFN-α) is a first line option in the treatment of chronic hepatitis B. Compared with nucleos(t)ide analogues (NAs), therapy with PEG-IFN-α has the advantages of finite treatment duration and higher rates of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion, but the disadvantage of greater adverse effects. Choosing PEG-IFN-α requires careful evaluation of the likelihood of achieving a sustained off-treatment response. Sustained off-treatment response with PEG-IFN-α can be predicted by baseline factors in HBeAg positive disease. These include genotype A or B, low viral load, high alanine aminotransferase (ALT), older age and female gender. On the other hand, no pre-treatment factors have been identified that can reliably predict response in HBeAg negative disease. Using on-treatment quantitative HBsAg levels, failure of a long term response can be identified with high negative predictive value (NPV). However, no combination of on treatment parameters have been identified so far that can precisely forecast successful treatment. Up until recently, there was little evidence supporting the use of combining PEG-IFN with NAs. The addition of PEG-IFN in patients who already have viral suppression with NAs therapy appears superior to continuing NAs alone in achieving a sustained response. Also, tenofovir disoproxil fumarate (TDF) in combination with PEG-IFN has been reported to enable significantly higher HBsAg loss than with either monotherapy alone. This occurred in both HBeAg positive and negative patients across all genotypes. In spite of recent developments, rates of HBsAg loss are still only in the order of 10% and so cure remains elusive. Further research is required to identify the optimal combination or sequential therapy regimen, and the subgroups with the highest rates of response so that they can be targeted.


hSETD1A regulates Wnt target genes and controls tumor growth of colorectal cancer cells.
hSETD1A is a member of the trithorax (TrxG) family of histone methyltransferases (HMT) that methylate H3K4 at promoters of active genes. Although misregulation of mixed lineage leukemia (MLL) family proteins has been associated with acute leukemia, the role of hSETD1A in cancer remains unknown. In this study, we report that hSETD1A and its associated H3K4me3 are upregulated in human colorectal cancer cells and patient samples. Depletion of hSETD1A inhibits colorectal cancer cell growth, colony formation, and tumor engraftment. Genome-wide expression profiling of colorectal cancer cells reveals that approximately 50% of Wnt/β-catenin target genes are affected by the hSETD1A knockdown. We further demonstrate that hSETD1A is recruited to promoters of those Wnt signaling target genes through its interaction with β-catenin, a master regulator of the Wnt signaling pathway. The recruitment of the hSETD1A HMT complex confers promoter-associated H3K4me3 that leads to assembly of transcription preinitiation complex and transcriptional activation. Furthermore, the expression levels of hSETD1A are positively correlated with H3K4me3 enrichment at the promoters of Wnt/β-catenin target genes and the aberrant activation of these genes in human colorectal cancer. These results provide new biologic and mechanistic insights into the cooperative role of hSETD1A and β-catenin in regulation of Wnt target genes as well as in colorectal cancer cell growth in vitro and in vivo.


The impact of protein oxidation on sustained and white coat hypertension.
The present study compared the unfavorable effects of protein oxidation and deoxyribonucleic acid damage on patients with white coat hypertension (WCH), sustained hypertension (HT), and normotensives. Participants were allocated into 3 groups: 40 healthy controls, 36 patients with WCH, and 40 patients with sustained HT. Patients with risk factors for atherosclerosis, endocrine diseases, alcoholism, or masked hypertension were excluded. Plasma level of protein carbonyl (PCO), ischemia modified albumin (IMA), total thiol (T-SH), prooxidant-antioxidant balance (PAB), advanced protein oxidation products (AOPPs), and urinary level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured and relationship between these oxidative stress parameters and WCH and sustained HT was analyzed. Ambulatory 24-hour, daytime and night-time systolic and diastolic blood pressure readings of sustained HT group were significantly higher than those of WCH and control groups (p<0.001, all). AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher in HT group than WCH and control groups (p<0.001, all). Additionally, T-SH level was significantly lower in HT group than WCH and control groups (p<0.001). A similar statistically significant relationship was detected between WCH and control groups. Results indicate that increased level of AOPPs, PCO, IMA, 8-OHdG, PAB, and decreased level of T-SH are likely to be indicators of oxidative stress, which may play a key role both in WCH and sustained HT.


The mutator form of polymerase beta with amino acid substitution at tyrosine 265 in the hinge region displays an increase in both base substitution and frame shift errors.
This study describes the first complete in vitro error specificity analysis of a mutator DNA polymerase that is altered in a residue not predicted to contact either the DNA or dNTP substrate. We examined this mutator form of polymerase beta (Y265C) in order to elucidate the critical role tyrosine 265 plays in the accuracy of DNA synthesis. Our results demonstrate that an increase in both frame shift errors in homonucleotide repeat sequences and base substitution errors contribute nearly equally to the Y265C mutator phenotype. The models described for production of these errors, primer/template misalignment and base misincorporation, respectively, are distinctly different, suggesting the Y265C alteration affects discrimination against both types of error production pathways. In addition, Y265C displays a 530-fold increase in multiple errors within the 203-base pair target region examined, relative to that of wild type. Processivity studies revealed that Y265C retains the near distributive nature of DNA synthesis characteristic of the wild type polymerase beta. Therefore, multiple errors exhibited by Y265C most likely result from independent polymerase binding events. Localization of tyrosine 265 in the X-ray crystallographic structure suggests this residue may play a role in mediating a conformational change of the polymerase [Pelletier, H., et al. (1996) Biochemistry 35, 12742-12761]. A conformational change is predicted to enhance the accuracy of DNA synthesis by imposing an induced fit selection against premutational intermediates. The observed loss of discrimination against both misalignment-mediated and misincorporation-mediated errors produced by polymerase Y265C is consistent with such a model.


Who takes risks in high-risk sport?: the role of alexithymia.
People who have difficulty identifying and describing their emotions are more likely to seek out the experience of emotions in the high-risk domain. This is because the high-risk domain provides the experience of more easily identifiable emotions (e.g., fear). However, the continued search for intense emotion may lead such individuals to take further risks within this domain, which, in turn, would lead to a greater likelihood of experiencing accidents. Across three studies, we provide the first evidence in support of this view. In Study 1 (n = 762), alexithymia was associated with greater risk taking and a greater propensity to experience accidents and close calls. In Study 2 (n = 332) and Study 3 (n = 356), additional bootstrapped mediation models confirmed these relationships. The predictive role of alexithymia remained significant when controlling for sensation seeking (Study 1) and anhedonia (Study 2 and Study 3). We discuss the practical implications of the present model as they pertain to minimizing accidents and close calls in the high-risk domain.


Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking.
Semiconductor quantum dots (QDs) are nanometer-sized fluorescent probes suitable for advanced biological imaging. We used QDs to track individual glycine receptors (GlyRs) and analyze their lateral dynamics in the neuronal membrane of living cells for periods ranging from milliseconds to minutes. We characterized multiple diffusion domains in relation to the synaptic, perisynaptic, or extrasynaptic GlyR localization. The entry of GlyRs into the synapse by diffusion was observed and further confirmed by electron microscopy imaging of QD-tagged receptors.


Effectiveness of community-based rehabilitation interventions incorporating outdoor mobility on ambulatory ability and falls-related self-efficacy after hip fracture: a systematic review and meta-analysis.
There is limited evidence from 11 randomised controlled trials on the effect of rehabilitation interventions which incorporate outdoor mobility on ambulatory ability and/or self-efficacy after hip fracture. Outdoor mobility should be central (not peripheral) to future intervention studies targeting improvements in ambulatory ability. Determine the extent to which outdoor mobility is incorporated into rehabilitation interventions after hip fracture. Synthesise the evidence for the effectiveness of these interventions on ambulatory ability and falls-related self-efficacy. Systematic search of MEDLINE, Embase, PsychInfo, CINAHL, PEDro and OpenGrey for published and unpublished randomised controlled trials (RCTs) of community-based rehabilitation interventions incorporating outdoor mobility after hip fracture from database inception to January 2021. Exclusion of protocols, pilot/feasibility studies, secondary analyses of RCTs, nonrandomised and non-English language studies. Duplicate screening for eligibility, risk of bias, and data extraction sample. Random effects meta-analysis. Statistical heterogeneity with inconsistency-value (I2). RCTs (n = 11) provided limited detail on target or achieved outdoor mobility intervention components. There was conflicting evidence from 2 RCTs for the effect on outdoor walking ability at 1-3 months (risk difference 0.19; 95% confidence intervals (CI): 0.21, 0.58; I2 = 92%), no effect on walking endurance at intervention end (standardised mean difference 0.05; 95% CI: - 0.26, 0.35; I2 = 36%); and suggestive (CI crosses null) of a small effect on self-efficacy at 1-3 months (standardised mean difference 0.25; 95% CI: - 0.29, 0.78; I2 = 87%) compared with routine care/sham intervention. It was not possible to attribute any benefit observed to an outdoor mobility intervention component due to poor reporting of target or achieved outdoor mobility and/or quality of the underlying evidence. Given the low proportion of patients recovering outdoor mobility after hip fracture, future research on interventions with outdoor mobility as a central component is warranted. PROSPERO registration: CRD42021236541.


The effects of alternate polypurine tracts (PPTs) and mutations of sequences adjacent to the PPT on viral replication and cleavage specificity of the Rous sarcoma virus reverse transcriptase.
We previously reported that a mutant Rous sarcoma virus (RSV) with an alternate polypurine tract (PPT), DuckHepBFlipPPT, had unexpectedly high titers and that the PPT was miscleaved primarily at one position following a GA dinucleotide by the RNase H of reverse transcriptase (RT). This miscleavage resulted in a portion of the 3' end of the PPT (5'-ATGTA) being added to the end of U3 of the linear viral DNA. To better understand the RNase H cleavage by RSV RT, we made a number of mutations within the DuckHepBFlipPPT and in the sequences adjacent to the PPT. Deleting the entire ATGTA sequence from the DuckHepBFlipPPT increased the relative titer to wild-type levels, while point mutations within the ATGTA sequence reduced the relative titer but had minimal effects on the cleavage specificity. However, mutating a sequence 5' of ATGTA affected the relative titer of the virus and caused the RNase H of RSV RT to lose the ability to cleave the PPT specifically. In addition, although mutations in the conserved stretch of thymidine residues upstream of the PPT did not affect the relative titer or cleavage specificity, the mutation of some of the nucleotides immediately upstream of the PPT did affect the titer and cleavage specificity. Taken together, our studies show that the structure of the PPT in the context of the cognate RT, rather than a specific sequence, is important for the proper cleavage by RSV RT.


Chemical composition and antifungal activity of Salvia macrochlamys and Salvia recognita essential oils.
Essential oils of Salvia macrochlamys and Salvia recognita were obtained by hydrodistillation of dried aerial parts and characterized by gas chromatography and gas chromatography-mass spectrometry. One hundred and twenty identified constituents representing 97.7% in S. macrochlamys and 96.4% in S. recognita were characterized, and 1,8-cineole, borneol, and camphor were identified as major components of the essential oils. The oils were evaluated for their antimalarial, antimicrobial, and antifungal activities. Antifungal activity of the essential oils from both Salvia species was nonselective at inhibiting growth and development of reproductive stroma of the plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. S. macrochlamys oil had good antimycobacterial activity against Mycobacterium intracellulare; however, the oils showed no antimicrobial activity against human pathogenic bacteria or fungi up to a concentration of 200 microg/mL. S. recognita oil exhibited a weak antimalarial activity against Plasmodium falciparum.


Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly.
Somatostatin receptor subtype 2 (sst2A) protein expression has been demonstrated to positively correlate with somatostatin analog treatment outcome in GH-secreting adenomas. Recently, a new rabbit monoclonal anti-sst2A antibody (clone UMB-1) has been validated as a reliable method to selectively detect sst2A protein levels in formalin-fixed tissues. The aim of the study was to establish whether the evaluation of sst2A protein levels, assessed with a routine reproducible immunohistochemistry protocol using UMB-1 antibody, may predict the successful adjuvant therapy with somatostatin analogs in acromegalic patients. Thirty-six acromegalic patients from our referral hospital were evaluated retrospectively. Sst2A expression analysis was performed by immunohistochemistry in 25 patients and by quantitative RT-PCR in 26 patients. Sst2A immunoreactivity was evaluated using an immunoreactivity score (IRS), which takes into account both the percentage of positive cells and staining intensity. Patients with persistent disease after surgery (n = 26) were treated with somatostatin analogs for a median duration of 6 months. GH and IGF-I levels were measured before and after postoperative treatment. Sst2A IRS showed a significant positive correlation with both GH (P = 0.039) and IGF-I (P = 0.001) suppression by octreotide. Sst2A IRS was negatively associated with IGF-I levels reached after treatment (P = 0.001), and patients that achieved IGF-I normalization showed significantly higher sst2A IRS compared to the group that was not normalized (P = 0.002). A sst2A IRS of at least 5 showed a sensitivity of 86% and a specificity of 91% in predicting IGF-I normalization during adjuvant octreotide treatment. Sst2A IRS with the anti-sst2A antibody UMB-1 represents a valid tool in the clinical practice to identify acromegalic patients likely to be responders to adjuvant therapy with the currently available somatostatin analogs.


The Role of Clinical Symptoms in the Diagnosis of Intrathoracic Tuberculosis in Young Children.
Childhood tuberculosis (TB) is usually Mycobacterium tuberculosis (MTB) culture negative. Furthermore, clinical presentation may be altered by active case finding, isoniazid prophylaxis and early treatment. We aimed to establish the value of presenting symptoms for intrathoracic TB case diagnosis among young children. Healthy, HIV-uninfected, South African infants in an efficacy trial of a novel TB vaccine (MVA85A) were followed for 2 years for suspected TB. When suspected, investigation followed a standardized algorithm comprising symptom history, QuantiFERON Gold-in-Tube, chest radiography (CXR), MTB culture and Xpert MTB/RIF from paired gastric lavage and induced sputa. Adjusted odds ratios and 95% confidence intervals describe the associations between symptoms and positive MTB culture or Xpert MTB/RIF, and CXR compatible with intrathoracic TB. Persistent cough was present in 172/1017 (16.9%) of the children investigated for TB. MTB culture/Xpert MTB/RIF was positive in 38/1017 children (3.7%); and CXR was positive, that is, compatible with intrathoracic TB, in 131/1017 children (12.9%). Children with persistent cough had more than triple the odds of a positive MTB culture/Xpert MTB/RIF (adjusted odds ratios: 3.3, 95% confidence interval: 1.5-7.0) and positive CXR (adjusted odds ratios: 3.5, 95% confidence interval: 2.2-5.5). Persistent cough was the only symptom that differentiated children with severe (56.5%) from nonsevere intrathoracic TB disease (28.2%; P = 0.001). Persistent cough was the cardinal diagnostic symptom associated with microbiologic and radiologic evidence, and disease severity, of intrathoracic TB. Symptom-based definitions of TB disease for diagnostic, preventive and therapeutic studies should prioritize persistent cough above other symptoms compatible with childhood TB.


Reliability of a Virtual Prosthodontic Project Realized through a 2D and 3D Photographic Acquisition: An Experimental Study on the Accuracy of Different Digital Systems.
The study aims to assess the accuracy of digital planning in dentistry, evaluating the characteristics of different intraoral 3D scanners and comparing it with traditional imaging 2D recording methods. Specifically, using computer aided design (CAD) software and measuring inside CAD software, authors want to verify the reliability of different models obtained with different techniques and machines. 12 patients that needed aesthetic restorative treatment were enrolled in the study. All the patients underwent recording data of the height and width dental elements 1.1, 1.2, and 1.3 size using different technologies and comparing 2D with 3D methods. A T test was then applied in order to verify whether there was a statistically significant difference between the measurements obtained, comparing the different tools data (Emerald, TRIOS, Photogrammetry and DSS (Digital Smile System)) with the reference values. No significant differences emerged in the measurements made with the different scanners (Trios 3Shape ®, Planmeca Emerald ®) and photogrammetry. Therefore, what should be underlined regarding the 2D measurements is the speed and simplicity compared to all 3D techniques, so this work can help to better define the field of application and the limits connected to 2D techniques, giving a good window of the technique. The low number of patients is not sufficient to provide statistically significant results, but the digital planning future prospects seem to be promising. This study results highlighted how a photogrammetric scanner for dental arches would only have a much smaller shooting field size and greater accuracy. Despite these considerations, the photogrammetric facial scanner provided excellent results for the measurement of individual teeth, showing a great versatility of use.


Stability of Biological Membranes upon Mechanical Indentation.
Mechanical perturbations are ubiquitous in living cells, and many biological functions are dependent on the mechanical response of lipid membranes. Recent force-spectroscopy studies have captured the stepwise fracture of stacks of bilayers, avoiding substrate effects. However, the effect of stacking bilayers, as well as the exact molecular mechanism of the fracture process, is unknown. Here, we use atomistic and coarse-grained force-clamp molecular dynamics simulation to assess the effects of mechanical indentation on stacked and single bilayers. Our simulations show that the rupture process obeys the laws of force-activated barrier crossing, and stacking multiple membranes stabilizes them. The rupture times follow a log-normal distribution which allows the interpretation of membrane rupture as a pore-growth process. Indenter hydrophobicity determines the type of pore formation, the preferred dwelling region, and the resistance of the bilayer against rupture. Our results provide a better understanding of the nanomechanics underlying the plastic rupture of lipid membranes.


Saline irrigation for allergic rhinitis.
Allergic rhinitis is a common condition affecting both adults and children. Patients experience symptoms of nasal obstruction, rhinorrhoea, sneezing and nasal itching, which may affect their quality of life.Nasal irrigation with saline (salty water), also known as nasal douching, washing or lavage, is a procedure that rinses the nasal cavity with isotonic or hypertonic saline solutions. It can be performed with low positive pressure from a spray, pump or squirt bottle, with a nebuliser or with gravity-based pressure in which the person instils saline into one nostril and allows it to drain out of the other. Saline solutions are available over the counter and can be used alone or as an adjunct to other therapies. To evaluate the effects of nasal saline irrigation in people with allergic rhinitis. The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL; Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 November 2017. Randomised controlled trials (RCTs) comparing nasal saline irrigation, delivered by any means and with any volume, tonicity and alkalinity, with (a) no nasal saline irrigation or (b) other pharmacological treatments in adults and children with allergic rhinitis. We included studies comparing nasal saline versus no saline, where all participants also received pharmacological treatment (intranasal corticosteroids or oral antihistamines). We used the standard methodological procedures expected by Cochrane. Primary outcomes were patient-reported disease severity and a common adverse effect - epistaxis. Secondary outcomes were disease-specific health-related quality of life (HRQL), individual symptom scores, general HRQL, the adverse effects of local irritation or discomfort, ear symptoms (pain or pressure) and nasal endoscopy scores. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. We included 14 studies (747 participants). The studies included children (seven studies, 499 participants) and adults (seven studies, 248 participants). No studies reported outcomes beyond three months follow-up. Saline volumes ranged from 'very low' to 'high' volume. Where stated, studies used either hypertonic or isotonic saline solution.Nasal saline versus no saline treatmentAll seven studies (112 adults; 332 children) evaluating this comparison used different scoring systems for patient-reported disease severity, so we pooled the data using the standardised mean difference (SMD). Saline irrigation may improve patient-reported disease severity compared with no saline at up to four weeks (SMD -1.32, 95% confidence interval (CI) -1.84 to -0.81; 407 participants; 6 studies; low quality) and between four weeks and three months (SMD -1.44, 95% CI -2.39 to -0.48; 167 participants; 5 studies; low quality). Although the evidence was low quality the SMD values at both time points are considered large effect sizes. Subgroup analysis showed the improvement in both adults and children. Subgroup analyses for volume and tonicity were inconclusive due to heterogeneity.Two studies reported methods for recording adverse effects and five studies mentioned them. Two studies (240 children) reported no adverse effects (epistaxis or local discomfort) in either group and three only reported no adverse effects in the saline group.One study (48 children) reported disease-specific HRQL using a modified RCQ-36 scale. It was uncertain whether there was a difference between the groups at any of the specified time points (very low quality). No other secondary outcomes were reported.Nasal saline versus no saline with adjuvant use of intranasal steroids or oral antihistamines Three studies (40 adults; 79 children) compared saline with intranasal steroids versus intranasal steroids alone; one study (14 adults) compared saline with oral antihistamines versus oral antihistamines alone. It is uncertain if there is a difference in patient-reported disease severity at up to four weeks (SMD -0.60, 95% CI -1.34 to 0.15; 32 participants; 2 studies; very low quality) or from four weeks to three months (SMD -0.32, 95% CI -0.85 to 0.21; 58 participants; 2 studies; very low quality). Although none of the studies reported methods for recording adverse effects, three mentioned them: one study (40 adults; adjuvant intranasal steroids) reported no adverse effects (epistaxis or local discomfort) in either group; the other two only reported no adverse effects in the saline group.It is uncertain if saline irrigation in addition to pharmacological treatment improved disease-specific HRQL at four weeks to three months, compared with pharmacological treatment alone (SMD -1.26, 95% CI -2.47 to -0.05; 54 participants; 2 studies; very low quality). No other secondary outcomes were reported.Nasal saline versus intranasal steroidsIt is uncertain if there was a difference in patient-reported disease severity between nasal saline and intranasal steroids at up to four weeks (MD 1.06, 95% CI -1.65 to 3.77; 14 participants; 1 study), or between four weeks and three months (SMD 1.26, 95% CI -0.92 to 3.43; 97 participants; 3 studies), or indisease-specific HRQL between four weeks and three months (SMD 0.01, 95% CI -0.73 to 0.75; 83 participants; 2 studies). Only one study reported methods for recording adverse effects although three studies mentioned them. One (21 participants) reported two withdrawals due to adverse effects but did not describe these or state which group. Three studies reported no adverse effects (epistaxis or local discomfort) with saline, although one study reported that 27% of participants experienced local discomfort with steroid use. No other secondary outcomes were reported. Saline irrigation may reduce patient-reported disease severity compared with no saline irrigation at up to three months in both adults and children with allergic rhinitis, with no reported adverse effects. No data were available for any outcomes beyond three months. The overall quality of evidence was low or very low. The included studies were generally small and used a range of different outcome measures to report disease severity scores, with unclear validation. This review did not include direct comparisons of saline types (e.g. different volume, tonicity).Since saline irrigation could provide a cheap, safe and acceptable alternative to intranasal steroids and antihistamines further high-quality, adequately powered research in this area is warranted.


Low-loss hybrid plasmonic waveguide for compact and high-efficient photonic integration.
A new hybrid plasmonic waveguide is introduced and characterized in the paper. By coupling the photonic modes of a Si waveguide with the higher-order plasmonic modes of a silver nanowire, we demonstrate that the resultant hybrid modes possess small mode areas and long propagation distances, as well as high excitation efficiency (~90%) from the conventional dielectric modes. Such hybrid waveguides may find applications in the high-dense photonic integrations.


Postpartum lifestyle interventions among women with pre-eclampsia: a scoping review protocol.
Compared to women with normotensive pregnancies, women with a history of pre-eclampsia have a roughly fourfold increased risk of developing chronic arterial hypertension and a twofold increased risk of developing cardiovascular disease (CVD). Lifestyle changes, such as increased physical activity, weight loss, smoking cessation and healthy diet, are effective for CVD prevention in the general population. However, no scoping review or systematic review of postpartum lifestyle interventions among women with pre-eclampsia have, to our best knowledge, been performed. The objective of this scoping review is to provide an overview of the available research literature on postpartum lifestyle interventions to reduce the risk of CVD among women with pre-eclampsia. The protocol is based on the framework outlined by Arksey and O'Malley. Databases to be searched include: PubMed, Embase CINAHL and the JBI Database of Systematic Reviews and Implementation Reports. The search will be performed after the publication of this protocol (estimated to be 1 June 2020) and will be repeated 1 month prior to the submission for publication of the final review (estimated to be 1 January 2021). The review will consider studies that include women in the postpartum period (in particular, but not restricted to, the first 12 months after delivery), with a history of pre-eclampsia. Data will be extracted by two independent reviewers using a data extraction tool including specific details about the population, concept, context, study methods and key findings relevant to the review objective. Any disagreements between the reviewers will be resolved through discussion, or with a third reviewer. The extracted data will be presented in diagrammatic or tabular form that align with the objective of this scoping review. A narrative summary will accompany the tabulated and/or charted results and will describe how the results relate to the reviews objective and questions. Since all data will be obtained from publicly available materials, the proposed scoping review does not require ethical approval. The results will be submitted for publication in an open-access peer-reviewed journal and presented at relevant conferences.


Ultrabright red AIEgens for two-photon vascular imaging with high resolution and deep penetration.
Reported here is a successful strategy for the design of ultrabright red luminogens with aggregation-induced emission (AIE) features, donor-acceptor structures, and intense charge transfer effects. These luminogens show no aggregation caused emission quenching in the solid state and have high quantum efficiency. They can be fabricated into AIE dots by a simple nanoprecipitation procedure. The AIE dots exhibit high brightness, a large Stokes shift, good biocompatibility, satisfactory photostability, and a high two-photon absorption cross section. The AIE dots can be utilized as highly efficient fluorescent probes for in vivo deep-tissue imaging by a two-photon technique, which outperforms the one-photon technique under the same experimental conditions, in terms of penetration depth and image contrast. This is the first report of using highly emissive AIE dots for the accurate measurement of capillary diameters in mouse ears. Such a strategy sheds light on the development of efficient solid state red/NIR emitters for biological applications.


Synthesis and Evaluation of New Bifunctional Chelators with Phosphonic Acid Arms for Gallium-68 Based PET Imaging in Melanoma.
Due to the increasing use of generator-produced radiometal Gallium-68 (68Ga) in positron-emission tomography/computed tomography (PET/CT), reliable bifunctional chelators that can efficiently incorporate 68Ga3+ into biomolecules are highly desirable. In this study, we synthesized two new bifunctional chelators bearing one or two phosphonic acid functional groups, named p-SCN-PhPr-NE2A1P and p-SCN-PhPr-NE2P1A, with the aim of enabling facile production of 68Ga-based radiopharmaceuticals. Both chelators were successfully conjugated to LLP2A-PEG4, a very late antigen-4 (VLA-4) targeting peptidomimetic ligand, to evaluate their application in 68Ga-based PET imaging. NE2P1A-PEG4-LLP2A exhibited the highest 68Ga3+ binding ability with molar activity of 37 MBq/nmol under mild temperature and neutral pH. Excellent serum stability of 68Ga-NE2P1A-PEG4-LLP2A was observed, which was consistent with the result obtained from density functional theory calculation. The in vitro cell study showed that 68Ga-NE2P1A-PEG4-LLP2A had significantly longer retention in B16F10 cells comparing to the reported retention of 64Cu-NE3TA-PEG4-LLP2A, although the uptake was relatively lower. In the biodistribution and micro-PET/CT imaging studies, high tumor uptake and low background were observed after 68Ga-NE2P1A-PEG4-LLP2A was injected into mice bearing B16F10 tumor xenografts, making it a highly promising radiotracer for noninvasive imaging of VLA-4 receptors overexpressed in melanoma.


A report on parent involvement in planning a randomised controlled trial in neonatology and lactation - insights for current and future research.
Patient and Public Involvement (PPI) is a rich and valuable part of the process of planning, designing, carrying out and disseminating research. It is important to communicate PPI findings in detail so that the contributions of those involved are fully utilised and disseminated. The extended and iterative PPI process used within a neonatal randomised controlled trial related to the expression of breastmilk after very preterm birth is reported here. Seven iterative stages of PPI were used. Stage 1 was informal PPI using historical interaction with parents and publicly available resources. Stage 2 was an online questionnaire open to parents of premature babies and advertised via a charity collaborator. Stage 3 was partnership with a charity collaborator. Stage 4 was a set of online panels focusing on study design and documents. Stage 5 was an interactive exercise to modify the trial intervention. Stage 6 is the presence of PPI contributors on the trial steering committee. Stage 7 is a dissemination panel. At each stage attention was paid to the diversity of participants involved, with strategies to increase the involvement of parents from under-reached groups. Six hundred and seventy-five participants responded at Stage 2, six parents were involved at Stage 4 and 12 parents at Stage 5. PPI contributed to the choice of study question, outcomes and produced a set of questions for future research. PPI impacted on the study design, with specific emphasis on reducing participant distress related to lactation, and reducing the burden of being involved in research at a time of significant stress. PPI had a far-reaching influence on this neonatal randomised controlled trial during the planning and design phase, which reinforces the importance of PPI at the earliest stages of the research cycle. The online questionnaire format elicited an unexpectedly deep and broad pool of transferable insights, which will have an impact on future research focus and design in the area of lactation and prematurity. Approaches to increasing PPI involvement from under-reached populations are important and can be successful despite resource constraints.


European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing: developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology.
To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing cardiac pacing. Under the auspice of the Clinical Practice Guideline Quality Indicator Committee of the European Society of Cardiology (ESC), the Working Group for cardiac pacing QIs was formed. The Group comprised Task Force members of the 2021 ESC Clinical Practice Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy, members of the European Heart Rhythm Association, international cardiac device experts, and patient representatives. We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care by constructing a conceptual framework of the management of patients receiving cardiac pacing, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. Four domains of care were identified: (i) structural framework, (ii) patient assessment, (iii) pacing strategy, and (iv) clinical outcomes. In total, seven main and four secondary QIs were selected across these domains and were embedded within the 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization therapy. By way of a standardized process, 11 QIs for cardiac pacing were developed. These indicators may be used to quantify adherence to guideline-recommended clinical practice and have the potential to improve the care and outcomes of patients receiving cardiac pacemakers.


Using forward calculations of the magnetic field perturbation due to a realistic vascular model to explore the BOLD effect.
This paper assesses the reliability of the infinite cylinder model used previously in the literature to simulate blood oxygenation level dependent (BOLD) signal changes. A three-dimensional finite element method was applied to a realistic model of the cortical vasculature, and the results compared with those generated from a simple model of the vasculature as a set of independent, randomly oriented, infinite cylinders. The realistic model is based on scanning electron microscopy measurements of the terminal vascular bed in the superficial cortex of the rat. Good agreement is found between the two models with regard to the extravascular R(2)* and R(2) dependence on the cerebral blood volume and blood oxygenation fraction. Using the realistic model, it is also possible to gain further understanding of the relative importance of intravascular and extravascular BOLD contrast. A simple parameterisation of the dependence of the relaxation rates on relative cerebral blood volume and blood-tissue susceptibility difference was carried out, allowing discussion of the variation in the form of the haemodynamic response with field strength.


Influence of Nigella sativa fixed oil on some blood parameters and histopathology of skin in staphylococcal-infected BALB/c mice.
Nigella sativa has been used for a long time in Jordanian folk medicine to treat skin diseases like microbial infections and inflammation. Therefore, the present study was conducted to assess the healing efficacy of petroleum ether extract of Nigella sativa seeds (fixed oil) on staphylococcal-infected skin. Male BALB/c mice were infected with 100 microL of Staphylococcus aureus (ATCC 6538) suspension at a dose of 10(8) colony forming unit/mouse into shaved mild dorsal skin. Application of treatments for each group (100 microL sterile saline, 100 microL chloramphenicol (10 microg/mouse) and Nigella sativa fixed oil at a dose of 50, 100 or 150 microL/mouse) was performed at the site of infection twice a day for two consecutive days after 3 h of infection. At day 3 and 5 after infection, total White Blood Cells (WBCs) count; differential and absolute differential WBC counts and the number of viable bacteria present in the skin area were measured. At day 5 after infection, the animals were sacrificed and the histology of skin was examined. Results indicated that fixed oil of Nigella sativa seeds enhance healing of staphylococcal-infected skin by reducing total and absolute differential WBC counts, local infection and inflammation, bacterial expansion and tissue impairment. These effects provide scientific basis for the use of Nigella sativa in traditional medicine to treat skin infections and inflammations.


Specialisation patterns of medical graduates, University of Malawi College of Medicine, Blantyre.
To describe specialization patterns of medical graduates of the University of Malawi College of Medicine. Cross sectional study. Medical graduates of the University of Malawi College of Medicine. University of Malawi College of Medicine. Speciality choices, sources of funding for training, employer at time of graduate studies and country where specialist training obtained. Between 1991 and 2000, 60 (35.5%) of the 169 graduates of the College of Medicine of the University of Malawi have obtained or are in specialist training, 38/60 (63.3%) with training institutions either in the United States or the United Kingdom, 10 (16.7%) had gone to South Africa, 8% Kenya, 5% to the Republic of China (Taiwan) and 3.3% to Uganda. Other countries are; Uganda, Australia and Finland. The preferred specialties were; Public Health 17 (28.8%), Internal Medicine 12 (20%) and Paediatrics 10 (16.7%). Most of the funding was provided by agencies/institutions in the USA and UK. At the time of their training fellowship, 33 (55%) of the candidates were employed by the College of Medicine, 24 (40%) by the public service and the rest, three (5%) by other institutions. Most Malawian medical graduates are obtaining their specialty training overseas funded mostly by institutions/agencies in the UK and USA. There is need to explore ways on how training could be provided regionally. Malawi and her neighbours must develop post graduate speciality training locally and regionally.


Novel photochemistry of molecular polaritons in optical cavities.
Violations of the Born-Oppenheimer approximation (BOA) and the consequent nonadiabatic dynamics have long been an object of intense study. Recently, such dynamics have been induced via strong coupling of the molecule to a high-amplitude (spatially confined) mode of the electromagnetic field in optical cavities. However, the effects of a cavity on a pre-existing avoided crossing or conical intersection are relatively unexplored. The dynamics of molecules dressed by cavity modes are usually calculated by invoking the rotating wave approximation (RWA), which greatly simplifies the calculation but breaks down when the cavity mode frequency is higher than the relevant material frequencies. We develop a protocol for computing curve crossing dynamics in an optical cavity by exploiting a recently-developed method of solving the quantum Rabi model without invoking the RWA. The method is demonstrated for sodium iodide.


Hospital based massage therapy specific competencies.
As massage therapy experiences a resurgence of use for hospitalized patients, it is appropriate to consider the competencies needed by practitioners to practice safely and effectively in the inpatient setting. Hospitals differ vastly from other massage practice locations such as private offices, spas, and sports clubs. The variety of conditions encountered in an acute care setting require the knowledge and ability to adapt massage protocols appropriately. The Academic Collaborative for Integrative Health (ACIH) created the Hospital Based Massage Therapy (HBMT) Task Force to determine if there is a need for HBMT specific competencies and then, if needed, to develop peer reviewed competencies that hospital staff, massage therapy educators, and massage therapists all may find useful. The members of the task force identified massage therapists who worked in hospitals generally, as well as in hospitals known to have HBMT programs. A spreadsheet was created listing the individuals and a survey was distributed to those on the spreadsheet. These individuals were also asked to identify others who might be interested in participating in the project. The purpose of the survey was to assess various elements of HBMT programs such as educational/experience requirements, employment model, orientation, and supervision. 32 out of 37 hospitals (87%) completed the survey. The Task Force considered the high response rate and the extent to which respondents provided in-depth answers to the open-ended questions as evidence of the need for specific competencies for safe and effective massage therapy for hospitalized patients. In addition to the survey, the task force used a Delphi technique to engage survey participants and other experts in the field to shape the initial draft of the competencies. As these competencies are shared with hospitals, massage therapists, and massage educators, the Task Force members expect that additional development of the competencies will take place as various groups implement them.


The environmental-data automated track annotation (Env-DATA) system: linking animal tracks with environmental data.
The movement of animals is strongly influenced by external factors in their surrounding environment such as weather, habitat types, and human land use. With advances in positioning and sensor technologies, it is now possible to capture animal locations at high spatial and temporal granularities. Likewise, scientists have an increasing access to large volumes of environmental data. Environmental data are heterogeneous in source and format, and are usually obtained at different spatiotemporal scales than movement data. Indeed, there remain scientific and technical challenges in developing linkages between the growing collections of animal movement data and the large repositories of heterogeneous remote sensing observations, as well as in the developments of new statistical and computational methods for the analysis of movement in its environmental context. These challenges include retrieval, indexing, efficient storage, data integration, and analytical techniques. This paper contributes to movement ecology research by presenting a new publicly available system, Environmental-Data Automated Track Annotation (Env-DATA), that automates annotation of movement trajectories with ambient atmospheric observations and underlying landscape information. Env-DATA provides a free and easy-to-use platform that eliminates technical difficulties of the annotation processes and relieves end users of a ton of tedious and time-consuming tasks associated with annotation, including data acquisition, data transformation and integration, resampling, and interpolation. The system is illustrated with a case study of Galapagos Albatross (Phoebastria irrorata) tracks and their relationship to wind, ocean productivity and chlorophyll concentration. Our case study illustrates why adult albatrosses make long-range trips to preferred, productive areas and how wind assistance facilitates their return flights while their outbound flights are hampered by head winds. The new Env-DATA system enhances Movebank, an open portal of animal tracking data, by automating access to environmental variables from global remote sensing, weather, and ecosystem products from open web resources. The system provides several interpolation methods from the native grid resolution and structure to a global regular grid linked with the movement tracks in space and time. The aim is to facilitate new understanding and predictive capabilities of spatiotemporal patterns of animal movement in response to dynamic and changing environments from local to global scales.


Premenstrual syndrome: an evolutionary perspective on its causes and treatment.
Premenstrual syndrome is a collection of heterogeneous symptoms that are attributed to hormonal fluctuations and that vary among individuals for unknown reasons. We propose that much of what is labeled "premenstrual syndrome" is part of a broader set of infectious illnesses that are exacerbated by cyclic changes in immunosuppression, which are induced by cyclic changes in estrogen and progesterone. This cyclic defense paradigm accords with the literature on cyclic exacerbations of persistent infectious diseases and chronic diseases of uncertain cause. Similar exacerbations attributable to hormonal contraception implicate hormonal alterations as a cause of these changes. The precise timing of these cyclic exacerbations depends on the mechanisms of pathogenesis and immunological control of particular infectious agents. Insight into these mechanisms can be obtained by a comparison of timing of menstrual exacerbations with the timing of exacerbations associated with pregnancy.


MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.
The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.


Mechanical tension drives cell membrane fusion.
Membrane fusion is an energy-consuming process that requires tight juxtaposition of two lipid bilayers. Little is known about how cells overcome energy barriers to bring their membranes together for fusion. Previously, we have shown that cell-cell fusion is an asymmetric process in which an "attacking" cell drills finger-like protrusions into the "receiving" cell to promote cell fusion. Here, we show that the receiving cell mounts a Myosin II (MyoII)-mediated mechanosensory response to its invasive fusion partner. MyoII acts as a mechanosensor, which directs its force-induced recruitment to the fusion site, and the mechanosensory response of MyoII is amplified by chemical signaling initiated by cell adhesion molecules. The accumulated MyoII, in turn, increases cortical tension and promotes fusion pore formation. We propose that the protrusive and resisting forces from fusion partners put the fusogenic synapse under high mechanical tension, which helps to overcome energy barriers for membrane apposition and drives cell membrane fusion.


Immuno-neutralization of circulating relaxin does not alter the breast cancer-protective action of parity in MNU-treated rats.
Early pregnancy and childbirth protects women against future development of breast cancer by an unknown mechanism. Parity likewise reduces mammary cancer incidence in rats exposed to the carcinogen, N-methyl-N-nitrosourea (MNU), providing a model for the human phenomenon. We hypothesized that relaxin, a 6KD luteal mammotropic hormone of pregnancy, might be the anti-cancer pregnancy factor, and that induced relaxin deficiency during rat gestation would restore carcinogen sensitivity. Forty-one pregnant (age 50 days) and 25 age-matched virgin Sprague-Dawley rats were used. Relaxin deficiency was induced by injecting mouse monoclonal anti-rat relaxin antibody (MCA1) days 12-18 of gestation. Pregnant controls were injected with vehicle or mouse IgG on the same schedule. Because MCA1 disrupts parturition, all rats underwent cesarean section on day 22. At age 100 days, all rats were injected i.v. with MNU (50mg/Kg) and examined daily for tumors until euthanized at age 240 days. Mammary tumor incidence and frequency were significantly (p<0.01) reduced and tumor latency was increased (p<0.001) in primiparous as compared with virgin rats. However, tumor incidence, type, size and latency were similar in MCA1-treated and control primiparous rats. Thus, luteal relaxin does not appear to be the factor responsible for resistance to breast cancer.


Complement-activating IgM enhances the humoral but not the T cell immune response in mice.
IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, Cμ13, which only produces IgM unable to activate complement, has normal antibody responses. Moreover, the recently discovered murine IgM Fc receptor (FcµR or TOSO/FAIM3) was shown to affect antibody responses. This prompted the re-investigation of whether complement activation by specific IgM is indeed required for enhancement of antibody responses and whether the mutation in Cµ13 IgM also caused impaired binding to FcµR. The results show that IgM from Cµ13 and wildtype mice bound equally well to the murine FcµR. In spite of this, specific Cμ13 IgM administered together with sheep red blood cells or keyhole limpet hemocyanine was a very poor enhancer of the antibody and germinal center responses as compared with wildtype IgM. Within seconds after immunization, wildtype IgM induced deposition of C3 on sheep red blood cells in the blood. IgM which efficiently enhanced the T-dependent humoral immune response had no effect on activation of specific CD4(+) T cells as measured by cell numbers, cell division, blast transformation, or expression of the activation markers LFA-1 and CD44 in vivo. These observations confirm the importance of complement for the ability of specific IgM to enhance antibody responses and suggest that there is a divergence between the regulation of T- and B-cell responses by IgM.


Influence of land mosaic composition and structure on patchy populations: the case of the water vole (Arvicola sapidus) in Mediterranean farmland.
The ability of patchy populations to persist in human-dominated landscapes is often assessed using focal patch approaches, in which the local occurrence or abundance of a species is related to the properties of individual patches and the surrounding landscape context. However, useful additional insights could probably be gained through broader, mosaic-level approaches, whereby whole land mosaics with contrasting patch-network and matrix characteristics are the units of investigation. In this study we addressed this issue, analysing how the southern water vole (Arvicola sapidus) responds to variables describing patch-network and matrix properties within replicated Mediterranean farmland mosaics, across a gradient of agricultural intensification. Patch-network characteristics had a dominant effect, with the total amount of habitat positively influencing both the occurrence of water voles and the proportion of area occupied in land mosaics. The proportions of patches and area occupied by the species were positively influenced by mean patch size, and negatively so by patch isolation. Matrix effects were weak, although there was a tendency for a higher proportion of occupied patches in more intensive, irrigated agricultural landscapes, particularly during the dry season. In terms of conservation, results suggest that water voles may be able to cope well with, or even be favoured by, the on-going expansion of irrigated agriculture in Mediterranean dry-lands, provided that a number of patches of wet herbaceous vegetation are maintained within the farmland mosaic. Overall, our study suggests that the mosaic-level approach may provide a useful framework to understand the responses of patchy populations to land use change.


2-Acetylcyclopentanone, an enolate-forming 1,3-dicarbonyl compound, is cytoprotective in warm ischemia-reperfusion injury of rat liver.
We have previously shown that 2-acetylcyclopentanone (2-ACP), an enolate-forming 1,3-dicarbonyl compound, provides protection in cell culture and animal models of oxidative stress. The pathophysiology of ischemia-reperfusion injury (IRI) involves oxidative stress, and, therefore, we determined the ability of 2-ACP to prevent this injury in a rat liver model. IRI was induced by clamping the portal vasculature for 45 minutes (ischemia phase), followed by recirculation for 180 minutes (reperfusion phase). This sequence was associated with substantial derangement of plasma liver enzyme activities, histopathological indices, and markers of oxidative stress. The 2-ACP (0.80-2.40 mmol/kg), administered by intraperitoneal injection 10 minutes prior to reperfusion, provided dose-dependent cytoprotection, as indicated by normalization of the IRI-altered liver histologic and biochemical parameters. The 2-ACP (2.40 mmol/kg) was also hepatoprotective when injected before clamping the circulation (ischemia phase). In contrast, an equimolar dose of N-acetylcysteine (2.40 mmol/kg) was not hepatoprotective when administered prior to reperfusion. Our studies to date suggest that during reperfusion the enolate nucleophile of 2-ACP limits the consequences of mitochondrial-based oxidative stress through scavenging unsaturated aldehyde electrophiles (e.g., acrolein) and chelation of metal ions that catalyze the free radical-generating Fenton reaction. The ability of 2-ACP to reduce IRI when injected prior to ischemia most likely reflects the short duration of this experimental phase (45 minutes) and favorable pharmacokinetics that maintain effective 2-ACP liver concentrations during subsequent reperfusion. These results provide evidence that 2-ACP or an analog might be useful in treating IRI and other conditions that have oxidative stress as a common molecular etiology.


[Human exposure to mercury in the Brazilian Amazon: a historical perspective].
The objective of the present article was to present the most important data generated by a multicentric study carried out by Brazilian researchers who, with the support of national and international institutions, worked during the 1990s to describe human exposure to mercury in gold mining areas in the Brazilian Amazon. Three sets of procedures were followed with residents of the Tocantins and Xingu river basins: (1) clinical examination, based on a standardized protocol and performed by a single researcher, in order to identify five basic levels of contamination; (2) determination of mercury levels in blood, hair, and urine, using atomic absorption spectrophotometry (Xingu Project); and (3) investigation of genotoxicity by using four cytogenetic indicators. During the first stage, 41 individuals were studied. Mercury was found in miners and their family members. Contamination was significantly associated with occupation and showed a differential correlation with genotoxicity indicators. After that, the Xingu project, which encompassed 625 individuals, focused on 417 Kayapó natives from the Gorotire and Djudjetiktire villages; 142 miners; and 66 riverine individuals (ribeirinhos). The highest levels of methylmercury in hair and total mercury in blood and urine were found among the Indian population. Contamination with inorganic forms of mercury was also observed in the blood, hair, and urine of Indians. Following a specific recommendation from the World Health Organization, special attention was given to pregnant Gorotire and Djudjetiktire women, who, although not directly exposed to mercury vapors, showed considerable levels of mercury intoxication. Despite this worrisome scenario, a number of social achievements in the 1990s point to new standards of dignity in health care and of social ethics in Brazil that could benefit everyone, including the victims of environmental injury.


Pretyphoon panic attack history moderates the relationship between degree of typhoon exposure and posttyphoon PTSD and depression in a Vietnamese sample.
Predisaster risk factors are related to postdisaster psychopathology even at relatively low levels of disaster exposure. A history of panic attacks (PA) may convey risk for postdisaster psychopathology and has been linked to a wide range of psychiatric disorders in Western and non-Western samples. The present study examined the main and interactive effects of pretyphoon PA and level of typhoon exposure in the onset of posttyphoon posttraumatic stress disorder (PTSD), major depression (MDD), and generalized anxiety disorder (GAD) in a Vietnamese sample of typhoon survivors. Typhoon Xangsane interrupted a Vietnamese epidemiological mental health needs assessment, providing a rare opportunity for preand posttyphoon assessments. Hierarchical logistic regression analyses evaluated whether the main and interactive effects of typhoon exposure severity and PA history were significantly related to posttyphoon diagnoses, above and beyond age, health status, pretyphoon psychiatric screening results, and history of potentially traumatic events. PA history moderated the relationship between severity of typhoon exposure and posttyphoon PTSD and MDD, but not GAD. Specifically, greater degree of exposure to the typhoon was significantly related to increased likelihood of postdisaster PTSD and MDD among individuals without a history of PA, above and beyond variance accounted for by pretyphoon psychiatric screening results. Individuals with a history of PA evidenced greater risk for postdisaster PTSD and MDD regardless of severity of typhoon exposure. Preexisting PA may affect the nature of the relationship between disaster characteristics and prevalence of postdisaster PTSD and MDD within Vietnamese samples.


A comparison of performing tube feeding with the standard procedures at selected educational and treatment centers of Isfahan University of Medical Sciences, Iran.
Tube feeding is used for patients, who are not able to eat orally but their digestive system can digest food. This method is safe and economical for patients, maintains the functions of the digestive system and reduces the risk of infection and sepsis. However, incorrect administration of this method of feeding results in problems such as aspiration pneumonia, infection, diarrhea, NG tube obstruction, and etcetera. If tube feeding is performed according to its standard procedure, it can have a major role in reducing complications, providing adaptability and the desired lifestyle, reducing the duration of hospitalization, and reducing the relevant costs. This research is a descriptive-analytic cross-sectional study on 37 nurses who worked in the general surgery and neurology wards and fed patients suffering from gastrostomy. A valid and reliable checklist was used for data collection. To analyze the data, the descriptive statistical method (frequency and mean) and inferential method (paired t-test, Spearman Correlation Coefficient and variance Analysis with repetition of observations) were used. The findings showed that the mean score of measures in all the stages (before, during, and after administration) was significantly lower than the standard (p < 0.001). There was a significant reverse relation between the score of measures in all the three stages (before, during, and after administration), and work record and work experience in the ward. Furthermore, the mean score of measures in all the three stages was significantly different between female and male subjects (p value = 0.031), in that the mean score of women was higher than that of men. There was also a significant difference between the mean score of measures in all the three stages, and the employment status of samples; so that the mean score of provisionally employed personnel was higher than that of permanently employed personnel. The findings of the research showed that the mean score of measures before, during, and after administration of feeding through gastrostomy was lower than the standard (p < 0.001). Therefore, a gastroenterology advisor, a clinical nurse and a nutrition specialist should train the patients and their families, and the personnel about preparation and storage of food, method of administering food, protection of tube entrance and NG tube by considering the problems and complications arising from this type of feeding. Based on the findings of the present research, it is necessary to retrain the nurses and especially male nurses, nurses with more work experience, and permanently employed nurses in terms of correct performance of clinical nursing skills including this type of feeding.


Advances in Clinical Cardiology 2017: A Summary of Key Clinical Trials.
Numerous important cardiology clinical trials have been published or presented at major international meetings during 2017. This paper aims to summarize these trials and place them in clinical context. The authors reviewed clinical trials presented at major cardiology conferences during 2017 including the American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, European Society of Cardiology, European Association for the Study of Diabetes, Transcatheter Cardiovascular Therapeutics, and the American Heart Association. Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 75 key cardiology clinical trials were identified for inclusion. New interventional and structural cardiology data include left main bifurcation treatment strategy, multivessel disease management in cardiogenic shock, drug-eluting balloons for in-stent restenosis, instantaneous wave-free physiological assessment, new-generation stents (COMBO, Orsiro), transcatheter aortic valve implantation, and closure devices. New preventative cardiology data include trials of liraglutide, empagliflozin, PCSK9 inhibitors (evolocumab and bococizumab), inclisiran, and anacetrapib. Antiplatelet data include the role of uninterrupted aspirin therapy during non-cardiac surgery and dual antiplatelet therapy following coronary artery bypass grafting. New data are also included from fields of heart failure (levosimendan, spironolactone), atrial fibrillation (apixaban in DC cardioversion), cardiac devices (closed loop stimulation pacing for neuromediated syncope), and electrophysiology (catheter ablation for atrial fibrillation). This paper presents a summary of key clinical cardiology trials during the past year and should be of practical value to both clinicians and cardiology researchers.


The epidemiology and clinical characteristics of patients with newly diagnosed alcohol-related liver disease: results from population-based surveillance.
We describe the epidemiology of outpatients newly diagnosed with chronic alcoholic liver disease and describe predictors of cirrhosis and referral for specialty care. Alcohol is a major cause of liver disease in the United States. Most previous work has described hospitalized patients. Participants were identified through prospective population-based surveillance in gastroenterology practices Multnomah County, Oregon and New Haven County, Connecticut; and primary care and gastroenterology practices from Kaiser Permanente Northern California in Alameda County during 1999 to 2001. Patients were interviewed, a blood specimen obtained, and their medical record reviewed. We identified 82 patients from gastroenterology practices with newly diagnosed alcoholic liver disease. Their median age was 50.0 years. 72.0% were male and 79.3% were White. The median age at initiation of alcohol use was 17.0 years. 43.9% of patients had evidence of cirrhosis at the time of diagnosis. Only 40.2% reported alcohol as the cause of their liver disease. Patients with cirrhosis were more likely to be older, have a higher median number of years of heavy alcohol consumption, and to have been hospitalized for a liver-related complication than noncirrhotic patients. An additional 83 primary care patients were more likely to be older, to be drinking alcohol at study interview, and to not have cirrhosis than patients referred for gastroenterology care. Patients with alcoholic liver disease may present at a late stage and may not identify alcohol as a cause for their liver disease. Improved patient screening and education may limit morbidity and mortality.


Adaptive optics enhanced direct laser writing of high refractive index gyroid photonic crystals in chalcogenide glass.
Chiral gyroid photonic crystals are fabricated in the high refractive index chalcogenide glass arsenic trisulfide with an adaptive optics enhanced direct laser writing system. The severe spherical aberration imparted when focusing into the arsenic trisulfide is mitigated with a defocus decoupled aberration compensation technique that reduces the level of aberration that must be compensated by over an order of magnitude. The fabricated gyroids are shown to have excellent uniformity after our adaptive optics method is employed, and the transmission spectra of the gyroids are shown to have good agreement with numerical simulations that are based on a uniform and diffraction limited fabrication resolution.


Quantitative investigations of different vaccination policies for the control of congenital rubella syndrome (CRS) in the United Kingdom.
The paper examines predictions of the impact of various one-, two- and three-stage vaccination policies on the incidence of congenital rubella syndrome (CRS) in the United Kingdom with the aid of a mathematical model of the transmission dynamics of rubella virus. Parameter estimates for the model are derived from either serological data or case notifications, and special attention is given to the significance of age-related changes in the rate of exposure to rubella infection and heterogeneous mixing between age groups. Where possible, model predictions are compared with observed epidemiological trends. The principal conclusion of the analyses is that benefit is to be gained in the UK, both in the short and long term, by the introduction of a multiple-stage vaccination policy involving high levels of vaccination coverage of young male and female children (at around two years of age) and teenage girls (between the ages of 10-15 years), plus continued surveillance and vaccination of adult women in the child-bearing age classes. Model predictions suggest that to reduce the incidence of CRS in future years, below the level generated by a continuation of the current UK policy (the vaccination of teenage girls), would require high rates of vaccination (greater than 60%) of both boys and girls at around two years of age. Numerical studies also suggest that uniform vaccination coverage levels of greater than 80-85% of young male and female children could, in the long term (40 years or more), eradicate rubella virus from the population. The robustness of these conclusions with respect to the accuracy of parameter estimates and various assumptions concerning the pattern of age-related change in exposure to infections and 'who acquires infection from whom' is discussed.


Blunted myocardial oxygenation response during vasodilator stress in patients with hypertrophic cardiomyopathy.
This study sought to assess myocardial perfusion and tissue oxygenation during vasodilator stress in patients with overt hypertrophic cardiomyopathy (HCM), as well as in HCM mutation carriers without left ventricular (LV) hypertrophy, and to compare findings to those in athletes with comparable hypertrophy and normal controls. Myocardial perfusion under vasodilator stress is impaired in patients with HCM. Whether this is associated with impaired myocardial oxygenation and tissue ischemia is unknown. Furthermore, it is not known whether perfusion and oxygenation are impaired in HCM mutation carriers without left ventricular hypertrophy (LVH). A total of 27 patients with overt HCM, 10 HCM mutation carriers without LVH, 11 athletes, and 20 healthy controls underwent cardiovascular magnetic resonance (CMR) scanning at 3-T. Myocardial function, perfusion (perfusion reserve index [MPRI]), and oxygenation (blood-oxygen level dependent signal intensity [SI] change) under adenosine stress were assessed. MPRI was significantly reduced in HCM (1.3 ± 0.1) compared to controls (1.8 ± 0.1, p < 0.001) and athletes (2.0 ± 0.1, p < 0.001), but remained normal in HCM mutation carriers without LVH (1.7 ± 0.1; p = 0.61 vs. controls, p = 0.02 vs. overt HCM). Oxygenation response was attenuated in overt HCM (SI change 6.9 ± 1.4%) compared to controls (18.9 ± 1.4%, p < 0.0001) and athletes (18.7 ± 2.0%, p < 0.001). Interestingly, HCM mutation carriers without LVH also showed an impaired oxygenation response to adenosine (10.4 ± 2.0%; p = 0.001 vs. controls, p = 0.16 vs. overt HCM, p = 0.003 vs. athletes). In overt HCM, both perfusion and oxygenation are impaired during vasodilator stress. However, in HCM mutation carriers without LVH, only oxygenation is impaired. In athletes, stress perfusion and oxygenation are normal. CMR assessment of myocardial oxygenation has the potential to become a novel risk factor in HCM.


Metal Modulation: An Easy-to-Implement Tactic for Tuning Lanthanide Phototheranostics.
Phototheranostics constitute an emerging cancer treatment wherein the core diagnostic and therapeutic functions are integrated into a single photosensitizer (PS). Achieving the full potential of this modality requires being able to tune the photosensitizing properties of the PS in question. Structural modification of the organic framework represents a time-honored strategy for tuning the photophysical features of a given PS system. Here we report an easy-to-implement metal selection approach that allows for fine-tuning of excited-state energy dissipation and phototheranostics functions as exemplified by a set of lanthanide (Ln = Gd, Yb, Er) carbazole-containing porphyrinoid complexes. Femto- and nanosecond time-resolved spectroscopic studies, in conjunction with density functional theory calculations, revealed that the energy dissipation pathways for this set of PSs are highly dependent on the energy gap between the lowest triplet excited state of the ligand and the excited states of the coordinated Ln ions. The Yb complex displayed a balance of deactivation mechanisms that made it attractive as a potential combined photoacoustic imaging and photothermal/photodynamic therapy agent. It was encapsulated into mesoporous silica nanoparticles (MSN) to provide a biocompatible construct, YbL@MSN, which displays a high photothermal conversion efficiency (η = 45%) and a decent singlet oxygen quantum yield (ΦΔ = 31%). Mouse model studies revealed that YbL@MSN allows for both photoacoustic imaging and synergistic photothermal- and photodynamic-therapy-based tumor reduction in vivo. Our results lead us to suggest that metal selection represents a promising approach to fine-tuning the excited state properties and functional features of phototheranostics.


Evaluation of School-Based Dental Sealant Programs: An Updated Community Guide Systematic Economic Review.
A recently updated Community Guide systematic review of the effectiveness of school sealant programs (SSPs) still found strong evidence that SSPs reduced dental caries among schoolchildren. This follow-up systematic review updates SSP cost and benefit information from the original 2002 review. Using Community Guide economic review methods, the authors searched the literature from January 2000 to November 20, 2014. The final body of evidence included 14 studies-ten from the current search and four with cost information from the 2002 review. Nine studies had information on SSP costs; six on sealant benefit (averted treatment costs and productivity losses); four on SSP net cost (cost minus benefit); and three on net cost to Medicaid of clinically delivered sealants. The authors imputed productivity losses and discounted costs/outcomes when this information was missing. The analysis, conducted in 2015, reported all values in 2014 U.S. dollars. The median one-time SSP cost per tooth sealed was $11.64. Labor accounted for two thirds of costs, and time to provide sealants was a major cost driver. The median annual economic benefit was $6.29, suggesting that over 4 years the SSP benefit ($23.37 at a 3% discount rate) would exceed costs by $11.73 per sealed tooth. In addition, two of four economic models and all three analyses of Medicaid claims data found that SSP benefit to society exceeded SSP cost. Recent evidence indicates the benefits of SSPs exceed their costs when SSPs target schools attended by a large number of high-risk children.


Complete chloroplast genome of Macadamia integrifolia confirms the position of the Gondwanan early-diverging eudicot family Proteaceae.
Sequence data from the chloroplast genome have played a central role in elucidating the evolutionary history of flowering plants, Angiospermae. In the past decade, the number of complete chloroplast genomes has burgeoned, leading to well-supported angiosperm phylogenies. However, some relationships, particulary among early-diverging lineages, remain unresolved. The diverse Southern Hemisphere plant family Proteaceae arose on the ancient supercontinent Gondwana early in angiosperm history and is a model group for adaptive radiation in response to changing climatic conditions. Genomic resources for the family are limited, and until now it is one of the few early-diverging 'basal eudicot' lineages not represented in chloroplast phylogenomic analyses. The chloroplast genome of the Australian nut crop tree Macadamia integrifolia was assembled de novo from Illumina paired-end sequence reads. Three contigs, corresponding to a collapsed inverted repeat, a large and a small single copy region were identified, and used for genome reconstruction. The complete genome is 159,714 bp in length and was assembled at deep coverage (3.29 million reads; ~2000 x). Phylogenetic analyses based on 83-gene and inverted repeat region alignments, the largest sequence-rich datasets to include the basal eudicot family Proteaceae, provide strong support for a Proteales clade that includes Macadamia, Platanus and Nelumbo. Genome structure and content followed the ancestral angiosperm pattern and were highly conserved in the Proteales, whilst size differences were largely explained by the relative contraction of the single copy regions and expansion of the inverted repeats in Macadamia. The Macadamia chloroplast genome presented here is the first in the Proteaceae, and confirms the placement of this family with the morphologically divergent Plantanaceae (plane tree family) and Nelumbonaceae (sacred lotus family) in the basal eudicot order Proteales. It provides a high-quality reference genome for future evolutionary studies and will be of benefit for taxon-rich phylogenomic analyses aimed at resolving relationships among early-diverging angiosperms, and more broadly across the plant tree of life.


Hard tick (Acari: Ixodidae) species of livestock and their seasonal activity in Boyer-Ahmad and Dena cities of Kohgiluyeh and Boyer-Ahmad Province, Southwest of Iran.
The present study was carried out to identify the Ixodidae ticks fauna of livestock and their seasonal activity in the cities of Boyer-Ahmad and Dena of Kohgiluyeh Province, south-west of Iran. Hard ticks from sheep, goats, and cattle were collected manually, stored in 70% ethanol, and identified using morphological characters. During the study, a total of 1273 hard ticks from four genera, including Rhipicephalus, Hyalomma, Dermacentor, and Haemaphysalis, were collected. Rhipicephalus sanguineus (s.l.) had the highest frequencies in both cities with 62.08 and 62.88% of collected specimens, followed by Hyalomma scupense with 14.36 and 13.54% in Boyer-Ahmad and Dena, respectively. Furthermore, Hyalomma marginatum with only one sample or 0.12% of collected ticks showed the lowest frequencies in the studied areas. Dermacentor marginatus with three samples or 0.37% was recorded only in Boyer-Ahmad, and Haemaphysalis sulcata with two samples or 0.43% was recorded only in Dena. In both cities, sheep were the most infested ruminant, and the ears in sheep and goats were the most affected areas. The highest activity was observed in spring, and the lowest activity was observed in winter and autumn. The results of the present study showed that Hyalomma and Rhipicephalus genera were the most widespread genera in the study areas. Regarding the importance of genera, such as Rhipicephalus, Hyalomma, and Haemaphysalis, in transmitting disease agents and the location of Kohgiloyeh and Boyer-Ahmad Province in the routes of migrant birds, further studies are required to elucidate their exact roles in human and livestock health in these areas.


Cannabinoid drugs: will they relieve or exacerbate tinnitus?
Recent enthusiasm for cannabinoid drugs for the treatment of chronic pain and some forms of epilepsy, raises the question of whether they could be useful for other disorders associated with abnormal neuronal activity in the brain, such as subjective tinnitus. Indeed, there is evidence to indicate that some tinnitus sufferers self-medicate using Cannabis. The aim of this review is to critically evaluate the available evidence relating to the effects of cannabinoids on tinnitus. Despite the fact that cannabinoids have been shown to decrease neuronal hyperactivity in many parts of the brain, the current evidence suggests that in auditory brain regions such as the dorsal cochlear nucleus, they have the potential to facilitate neuronal hyperactivity and exacerbate tinnitus. All of the available experimental evidence from animal studies suggests that cannabinoid CB1 receptor agonists will either have no effect on tinnitus or will worsen it. In our opinion, the use of the available cannabinoid drugs to alleviate tinnitus, based on their alleged efficacy for neuropathic pain conditions and some forms of epilepsy, is premature and not supported by the available evidence.


Rickettsia Detected in the Reptile Tick Bothriocroton hydrosauri from the Lizard Tiliqua rugosa in South Australia.
Rickettsiosis is a potentially fatal tick borne disease. It is caused by the obligate intracellular bacteria Rickettsia, which is transferred to humans through salivary excretions of ticks during the biting process. Globally, the incidence of tick-borne diseases is increasing; as such, there is a need for a greater understanding of tick-host interactions to create more informed risk management strategies. Flinders Island spotted fever rickettsioses has been identified throughout Australia (Tasmania, South Australia, Queensland and Torres Strait Islands) with possible identifications in Thailand, Sri Lanka and Italy. Flinders Island spotted fever is thought to be spread through tick bites and the reptile tick Bothriocroton hydrosauri has been implicated as a vector in this transmission. This study used qPCR to assay Bothriocroton hydrosauri ticks collected from Tiliqua rugosa (sleepy lizard) hosts on mainland South Australia near where spotted fever cases have been identified. We report that, although we discovered Rickettsia in all tick samples, it was not Rickettsia honei. This study is the first to use PCR to positively identify Rickettsia from South Australian Bothriocroton hydrosauri ticks collected from Tiliqua rugosa (sleepy lizard) hosts. These findings suggest that B. hydrosauri may be a vector of multiple Rickettsia spp. Also as all 41 tested B. hydrosauri ticks were positive for Rickettsia this indicates an extremely high prevalence within the studied area in South Australia.


Towards Automated Annotation of Benthic Survey Images: Variability of Human Experts and Operational Modes of Automation.
Global climate change and other anthropogenic stressors have heightened the need to rapidly characterize ecological changes in marine benthic communities across large scales. Digital photography enables rapid collection of survey images to meet this need, but the subsequent image annotation is typically a time consuming, manual task. We investigated the feasibility of using automated point-annotation to expedite cover estimation of the 17 dominant benthic categories from survey-images captured at four Pacific coral reefs. Inter- and intra- annotator variability among six human experts was quantified and compared to semi- and fully- automated annotation methods, which are made available at coralnet.ucsd.edu. Our results indicate high expert agreement for identification of coral genera, but lower agreement for algal functional groups, in particular between turf algae and crustose coralline algae. This indicates the need for unequivocal definitions of algal groups, careful training of multiple annotators, and enhanced imaging technology. Semi-automated annotation, where 50% of the annotation decisions were performed automatically, yielded cover estimate errors comparable to those of the human experts. Furthermore, fully-automated annotation yielded rapid, unbiased cover estimates but with increased variance. These results show that automated annotation can increase spatial coverage and decrease time and financial outlay for image-based reef surveys.


Tactile-kinesthetic stimulation effects on sympathetic and adrenocortical function in preterm infants.
The purpose of our study was to investigate the neuroendocrine response in preterm infants to a pattern of tactile-kinesthetic stimulation that facilitates their growth and development. Preterm infants (mean gestational age 30 weeks, mean birth weight 1176 gm) received normal nursery care or tactile-kinesthetic stimulation for three 15-minute periods at the start of three consecutive hours each day for 10 days. On day 1 and day 10 of the study, a 24-hour urine sample was collected for norepinephrine, epinephrine, dopamine, cortisol, and creatinine assay and a blood sample was taken by heel stick for cortisol and growth hormone assay. Urine norepinephrine and epinephrine values increased significantly only in the stimulated babies. Urine dopamine and cortisol values increased in both groups, and serum growth hormone decreased in both groups. Individual differences in urine norepinephrine, epinephrine, dopamine, and cortisol values were highly stable across the 10 days despite a 10-fold range of values among the infants. The results of this study suggest that tactile-kinesthetic stimulation of preterm infants has fairly specific effects on maturation and/or activity of the sympathetic nervous system. In addition, this study has defined catecholamine and cortisol secretion across gestational age in normal preterm infants. Finally, these data suggest that highly stable individual levels of catecholamine and cortisol secretion are established by birth in humans.


Terrorism and dispelling the myth of a panic prone public.
Governments and commentators perceive the public to be prone to panic in response to terrorist attacks--conventional or involving chemical, biological or radiological weapons. Evidence from five such incidents suggests that the public is not prone to panic, although people can change their behaviours and attitudes to reduce the risk of themselves being exposed to a terrorist incident. Behavioural responses may be divided into acts of omission, such as not making unnecessary journeys, and acts of commission, such as taking prophylactic medication despite the inherent risk of side effects. Evidence suggests that the public are aware of these differences, and tend to adopt responses proportionate to the risk. Drawing upon the literature in the social and natural sciences, our discussion encompasses differing risk perceptions of terrorist threats and consequences of attacks. How do fear and anxiety interact with behavioural responses to amplify or attenuate perceptions that can be modified through risk communication undertaken by authorities?


Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis patients and control subjects.
Ninety-eight subjects underwent methacholine (Mecholyl) aerosol challenge at a concentration of 5 mg/ml. All atopic groups differed significantly in their bronchial response to Mecholyl compared to nonatopic control subjects. Nineteen normal subjects had a mean decrease of 11.4% in forced expiratory volume in one second (FEV1) with 128 Mecholyl inhalations and 2 decreased by greater than 20%. Fifteen of 27 allergic rhinitis patients had a positive response to Mecholyl as defined by a decrease in FEV1 greater than 20%. Four of these responders developed greater diminution in FEV1 response with additional Mecholyl inhalations in a manner similar to that seen in the asthmatic patients. Eighteen current asthmatics showed the greatest bronchial sensitivity to Mecholyl with a mean 33% decrease in FEV1 at 4.5 inhalations. One hundred per cent of current asthmatics and 82% (28 of 34) of former asthmatics (free of asthma symptoms for 1 to 20 yr) showed positive response to Mecholyl. A 20% decrease in FEV1 with a total of 20 inhalations or less is consistent with a diagnosis of "current asthma," and even 20 of 34 former asthmatics responded in this manner. The Mecholyl aerosol test can be used to diagnose previous and current asthma and may be of value in predicting asthma in hay fever patients.


Mapping psychotic-like experiences: Results from an online survey.
Suggestions have been made that psychotic-like experiences (PLEs), such as hallucinatory and delusional experiences, exist on a continuum from healthy individuals to patients with a diagnosis of schizophrenia. We used the screening questions of the Questionnaire for Psychotic Experiences (QPE), an interview that captures the presence and phenomenology of various psychotic experiences separately, to assess PLEs in Norway. Based on data from an online survey in a sample of more than 1,400 participants, we demonstrated that the QPE screening questions show satisfactory psychometric properties. Participants with mental disorders reported more frequent lifetime and current hallucinatory experiences than participants without mental disorders. Childhood experiences were rather low and ranged from 0.7% to 5.2%. We further replicated findings that young age, illegal drug use, lower level of education, and having parents with a mental disorder are associated with higher endorsement rates of PLEs. Finally, a binomial regression revealed that the mere presence of PLEs does not discriminate between individuals with and without a mental disorder. Taken together, the findings of the present study support existing models that both hallucinations and delusions exist on a structural and phenomenological continuum. Moreover, we demonstrated that the QPE screening questions can be used by themselves as a complementary tool to the full QPE interview.


Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis.
There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies. Case-based surveys were administered to CARRA members to identify prevailing treatments for new-onset systemic JIA. A 2-day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Followup surveys were employed to refine the plans and assess clinical acceptability. The initial case-based survey identified significant variability among current treatment approaches for new-onset systemic JIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed 4 consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The 4 treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra, or tocilizumab, with or without glucocorticoids. This approach was approved by >78% of the CARRA membership. Four standardized treatment plans were developed for new-onset systemic JIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of systemic JIA.


Surface degradation of glass ceramics after exposure to acidulated phosphate fluoride.
This study evaluated the surface degradation effect of acidulated phosphate fluoride (APF) gel exposure on the glassy matrix ceramics as a function of time. Disc-shaped ceramic specimens (N = 120, 10/per ceramic material) were prepared in stainless steel molds (inner diameter: 5 mm, height: 2 mm) using 6 dental ceramics: 3 indicated for ceramic-fused-to-metal (Vita Omega 900, Carmen and Vita Titankeramik), 2 for all-ceramic (Vitadur Alpha and Finesse Low Fusing) and 1 for both types of restorations (IPS d.SIGN). The specimens were wet ground finished, ultrasonically cleaned and auto-glazed. All specimens were subjected to calculation of percentage of mass loss, surface roughness analysis and topographical description by scanning electron microscopy (SEM) before (0 min) and after exposure to 1.23 % APF gel for 4 min and 60 min representing short- and long-term etching effect, respectively. The data were analyzed using two-way ANOVA with repeated measures and Tukey's test (a=0.05). Significant effect of the type of the ceramics (p=0.0000, p=0.0031) and exposure time (p=0.0000) was observed in both surface roughness and percentage of mass loss values, respectively. The interaction factor between both parameters was also significant for both parameters (p=0.0904, p=0.0258). Both 4 min (0.44+/-0.1 - 0.81+/-0.2 microm) and 60 min (0.66+/-0.1 - 1.04+/-0.3 microm) APF gel exposure created significantly more surface roughness for all groups when compared to the control groups (0.33+/-0.2 - 0.68+/-0.2 microm) (p<0.05). There were no significant differences in percentage of mass loss between the ceramics at 4 min (p>0.05) but at 60 min exposure, IPS d.SIGN showed the highest percentage of mass loss (0.1151+/-0.11). The mean surface roughness for Vita Titankeramik (0.84+/-0.2 microm) and Finesse Low Fusing (0.74.+/-0.2 microm) was significantly higher than those of the other ceramics (0.59+/-0.1 microm - 0.49+/-0.1 microm) and Vita Titankeramik (p<0.05) regardless of the exposure time. A positive correlation was found between surface roughness and percentage of mass loss for all ceramic materials [(r=0.518 (Vitadur Alpha), r=0.405 (Vita Omega 900), r=0.580 (Carmen), r=0.687 (IPS d.SIGN), r=0.442 (Finesse Low Fusing), r=0.572 (Vita Titankeramik), Pearson's correlation coefficient)]. The qualitative SEM analysis showed evidence of corrosive attack on all of ceramics at varying degrees. The ceramics indicated for either metal-ceramic or all-ceramic restorations were all vulnerable to surface texture changes and mass loss after short-term and long-term APF gel exposure.


Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty.
Recent studies have shown that symptomatic venous thromboembolism after total hip arthroplasty most commonly develops after the patient is discharged from the hospital. Risk factors associated with these symptomatic thromboembolic events are not well defined. Using administrative data from the California Medicare records for 1993 through 1996, we identified 297 patients 65 years of age or older who were rehospitalized for thromboembolism within three months after total hip arthroplasty. We compared demographic, surgical, and medical variables potentially associated with the development of thromboembolism in these patients and 592 unmatched controls. A total of 89.6 percent of patients with thromboembolism and 93.8 percent of control patients were treated with pneumatic compression, warfarin, enoxaparin, or unfractionated heparin, alone or in combination. In addition, 22.2 percent and 29.7 percent, respectively, received warfarin after discharge. A body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or greater was associated with rehospitalization for thromboembolism, with an odds ratio of 2.5 (95 percent confidence interval, 1.8 to 3.4). In a multivariate model, the only prophylactic regimens associated with a reduced risk of thromboembolism were pneumatic compression in patients with body-mass indexes of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6) and warfarin treatment after discharge (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 1.0). In patients who underwent total hip arthroplasty, a body-mass index of 25 or greater was associated with subsequent hospitalization for thromboembolism. Pneumatic compression in patients with a body-mass index of less than 25 and prophylaxis with warfarin after discharge were independently protective against thromboembolism.


Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial.
Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays. Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham. Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.