Sleep-disordered breathing is associated with disturbed cardiac repolarization in patients with a coronary artery bypass graft surgery

Publication date: Available online 8 January 2018
Source:Sleep Medicine
Author(s): Christina Schmidleitner, Michael Arzt, Maria Tafelmeier, Sarah Ripfel, Miriam Fauser, Teresa Weizenegger, Bernhard Flörchinger, Daniele Camboni, Sigrid Wittmann, Florian Zeman, Christof Schmid, Lars S. Maier, Stefan Wagner, Christoph Fisser
BackgroundThe development of malignant ventricular arrhythmias due to abnormal cardiac repolarization is a major complication after coronary artery bypass graft surgery (CABG). Sleep-disordered breathing (SDB) is linked to prolonged cardiac repolarization in non-surgical patients. This study evaluates cardiac repolarization in patients with and without SDB who underwent CABG.Methods100 patients who had received CABG (84% men, age 68±10 years, body-mass-index [BMI] 28.7±4.2 kg/m²) were retrospectively evaluated. Polygraphy was recorded the night before CABG. SDB was defined as an apnea-hypopnea index (AHI) of ≥15/h and differentiated into central (CSA) and obstructive (OSA) sleep apnea. Cardiac repolarization was assessed by means of T-peak-to-end (TpTe) and QTc-intervals and TpTe/QT-ratios derived from 12-lead electrocardiography (ECG).Results37% of patients had SDB, 14% CSA and 23% OSA. Before CABG, patients with CSA and OSA had longer TpTe intervals than those without SDB (TpTe: CSA 100±26 vs. OSA 97±19 vs. no SDB 85±14ms, p=0.013). QTc intervals and TpTe/QT ratios differed between the two groups (QTc: 444±54 vs. 462±36 vs. 421±32ms, p<0.001; TpTe/QT ratio: 0.24±0.04 vs. 0.23±0.05 vs. 0.21±0.03, p=0.045). SDB was associated with abnormal cardiac repolarization independent of known risk factors for cardiac arrhythmias, such as age, sex, BMI, N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), and heart failure (TpTe: B-coefficient [95%-CI]: 16.0, [7.6-24.3], p<0.001; QTc: 27.2 [9.3-45.1], p=0.003; TpTe/QT ratio: 2.9 [1.2-4.6], p<0.001).ConclusionIndependent of known risk factors for cardiac arrhythmias, SDB was significantly associated with abnormal cardiac repolarization before CABG. Data suggest that SDB may contribute to an increased risk of ventricular arrhythmias after CABG.



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AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster

by Neeta Bala Tannan, Giovanna Collu, Ashley C. Humphries, Ekatherina Serysheva, Ursula Weber, Marek Mlodzik

AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF) mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

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An Ichor-dependent apical extracellular matrix regulates seamless tube shape and integrity

by Jeffrey B. Rosa, Mark M. Metzstein, Amin S. Ghabrial

During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens.

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AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster

by Neeta Bala Tannan, Giovanna Collu, Ashley C. Humphries, Ekatherina Serysheva, Ursula Weber, Marek Mlodzik

AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF) mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

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An Ichor-dependent apical extracellular matrix regulates seamless tube shape and integrity

by Jeffrey B. Rosa, Mark M. Metzstein, Amin S. Ghabrial

During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens.

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Does histology dictate outcomes of locally advanced rectal adenocarcinoma with complete pathological response following neoadjuvant chemoradiation?

Abstract

Introduction

Complete pathological response (pCR) is an independent prognostic factor for favorable outcome in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (NACTRT). Various studies have reported pCR rates of approximately 15–25%. Various predictive factors of pCR are described and these include tumor size, histological subtype, clinical stage at presentation, negative circumferential resection margin (CRM), different neoadjuvant regimen, and interval between NACTRT and surgery. Some histological subtypes like signet cell have historically been associated with poor outcome. However, there is no study that analyzes the impact of histological subtype after pCR has been achieved. We intended to assess the impact of histological subtype on long-term outcome in patients who have achieved pCR.

Patients and methods

Seventy-three consecutive patients of locally advanced rectal cancer, who had pCR after long-course NACTRT in the period between 2013 and 2015, were included in the analysis. The study population was grouped into three histological groups (signet, mucinous, and non-signet non-mucinous). These three groups were compared with respect to recurrence rate, recurrence pattern, disease-free survival (DFS), and overall survival (OS).

Results

The study cohort was divided into three groups—signet (16.4%), mucinous (24.6%), and non-signet non-mucinous adenocarcinoma (59%). Median age was 43 years and mean pre-treatment carcino-embryonic antigen level was 9.1 ng/ml. With a median follow-up time of 35 months, 3-year OS and DFS rates were found to be 92.5 and 75.3%, respectively. There was no significant difference in OS and DFS amongst the three groups.

Conclusion

Histological subtype does not affect the long-term outcomes in patients who achieve pathological complete response to preoperative chemoradiation.

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Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection

by Thamir Alandijany, Ashley P. E. Roberts, Kristen L. Conn, Colin Loney, Steven McFarlane, Anne Orr, Chris Boutell

Detection of viral nucleic acids plays a critical role in the induction of intracellular host immune defences. However, the temporal recruitment of immune regulators to infecting viral genomes remains poorly defined due to the technical difficulties associated with low genome copy-number detection. Here we utilize 5-Ethynyl-2'-deoxyuridine (EdU) labelling of herpes simplex virus 1 (HSV-1) DNA in combination with click chemistry to examine the sequential recruitment of host immune regulators to infecting viral genomes under low multiplicity of infection conditions. Following viral genome entry into the nucleus, PML-nuclear bodies (PML-NBs) rapidly entrapped viral DNA (vDNA) leading to a block in viral replication in the absence of the viral PML-NB antagonist ICP0. This pre-existing intrinsic host defence to infection occurred independently of the vDNA pathogen sensor IFI16 (Interferon Gamma Inducible Protein 16) and the induction of interferon stimulated gene (ISG) expression, demonstrating that vDNA entry into the nucleus alone is not sufficient to induce a robust innate immune response. Saturation of this pre-existing intrinsic host defence during HSV-1 ICP0-null mutant infection led to the stable recruitment of PML and IFI16 into vDNA complexes associated with ICP4, and led to the induction of ISG expression. This induced innate immune response occurred in a PML-, IFI16-, and Janus-Associated Kinase (JAK)-dependent manner and was restricted by phosphonoacetic acid, demonstrating that vDNA polymerase activity is required for the robust induction of ISG expression during HSV-1 infection. Our data identifies dual roles for PML in the sequential regulation of intrinsic and innate immunity to HSV-1 infection that are dependent on viral genome delivery to the nucleus and the onset of vDNA replication, respectively. These intracellular host defences are counteracted by ICP0, which targets PML for degradation from the outset of nuclear infection to promote vDNA release from PML-NBs and the onset of HSV-1 lytic replication.

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Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection

by Thamir Alandijany, Ashley P. E. Roberts, Kristen L. Conn, Colin Loney, Steven McFarlane, Anne Orr, Chris Boutell

Detection of viral nucleic acids plays a critical role in the induction of intracellular host immune defences. However, the temporal recruitment of immune regulators to infecting viral genomes remains poorly defined due to the technical difficulties associated with low genome copy-number detection. Here we utilize 5-Ethynyl-2'-deoxyuridine (EdU) labelling of herpes simplex virus 1 (HSV-1) DNA in combination with click chemistry to examine the sequential recruitment of host immune regulators to infecting viral genomes under low multiplicity of infection conditions. Following viral genome entry into the nucleus, PML-nuclear bodies (PML-NBs) rapidly entrapped viral DNA (vDNA) leading to a block in viral replication in the absence of the viral PML-NB antagonist ICP0. This pre-existing intrinsic host defence to infection occurred independently of the vDNA pathogen sensor IFI16 (Interferon Gamma Inducible Protein 16) and the induction of interferon stimulated gene (ISG) expression, demonstrating that vDNA entry into the nucleus alone is not sufficient to induce a robust innate immune response. Saturation of this pre-existing intrinsic host defence during HSV-1 ICP0-null mutant infection led to the stable recruitment of PML and IFI16 into vDNA complexes associated with ICP4, and led to the induction of ISG expression. This induced innate immune response occurred in a PML-, IFI16-, and Janus-Associated Kinase (JAK)-dependent manner and was restricted by phosphonoacetic acid, demonstrating that vDNA polymerase activity is required for the robust induction of ISG expression during HSV-1 infection. Our data identifies dual roles for PML in the sequential regulation of intrinsic and innate immunity to HSV-1 infection that are dependent on viral genome delivery to the nucleus and the onset of vDNA replication, respectively. These intracellular host defences are counteracted by ICP0, which targets PML for degradation from the outset of nuclear infection to promote vDNA release from PML-NBs and the onset of HSV-1 lytic replication.

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Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection

by Thamir Alandijany, Ashley P. E. Roberts, Kristen L. Conn, Colin Loney, Steven McFarlane, Anne Orr, Chris Boutell

Detection of viral nucleic acids plays a critical role in the induction of intracellular host immune defences. However, the temporal recruitment of immune regulators to infecting viral genomes remains poorly defined due to the technical difficulties associated with low genome copy-number detection. Here we utilize 5-Ethynyl-2'-deoxyuridine (EdU) labelling of herpes simplex virus 1 (HSV-1) DNA in combination with click chemistry to examine the sequential recruitment of host immune regulators to infecting viral genomes under low multiplicity of infection conditions. Following viral genome entry into the nucleus, PML-nuclear bodies (PML-NBs) rapidly entrapped viral DNA (vDNA) leading to a block in viral replication in the absence of the viral PML-NB antagonist ICP0. This pre-existing intrinsic host defence to infection occurred independently of the vDNA pathogen sensor IFI16 (Interferon Gamma Inducible Protein 16) and the induction of interferon stimulated gene (ISG) expression, demonstrating that vDNA entry into the nucleus alone is not sufficient to induce a robust innate immune response. Saturation of this pre-existing intrinsic host defence during HSV-1 ICP0-null mutant infection led to the stable recruitment of PML and IFI16 into vDNA complexes associated with ICP4, and led to the induction of ISG expression. This induced innate immune response occurred in a PML-, IFI16-, and Janus-Associated Kinase (JAK)-dependent manner and was restricted by phosphonoacetic acid, demonstrating that vDNA polymerase activity is required for the robust induction of ISG expression during HSV-1 infection. Our data identifies dual roles for PML in the sequential regulation of intrinsic and innate immunity to HSV-1 infection that are dependent on viral genome delivery to the nucleus and the onset of vDNA replication, respectively. These intracellular host defences are counteracted by ICP0, which targets PML for degradation from the outset of nuclear infection to promote vDNA release from PML-NBs and the onset of HSV-1 lytic replication.

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Stridor combined with other sleep breathing disorders in multiple system atrophy: A tailored treatment?

Publication date: Available online 8 January 2018
Source:Sleep Medicine
Author(s): Saleheddine Rekik, Francis Martin, Pauline Dodet, Stefania Redolfi, Smaranda Leu-Semenescu, Jean-Christophe Corvol, David Grabli, Isabelle Arnulf
ObjectivesTo determine the frequency of sleep breathing disorders in multiple systemic atrophy (MSA, combining Parkinsonism, cerebellar syndrome and dysautonomia) and evaluate the benefit/tolerance of various modes of ventilation.MethodsWe retrospectively analyzed 45 patients with MSA having undergone a videopolysomnography. Their sleep characteristics were compared to those of 45 patients with Parkinson's disease and 45 healthy controls, matched for age and sex. Patients with MSA received fixed continuous positive airway pressure (CPAP) when stridor was isolated, auto-adjusting CPAP when it was combined with obstructive sleep apnea, and adaptive servo-ventilation (ASV) when combined with central sleep apnea.ResultsHigher periodic leg movements index and more frequent REM sleep behavior disorder were observed in MSA patients, compared to patients with Parkinson's disease and healthy controls. In MSA, 28/45 (62.2%) patients had sleep breathing disorders, including (overlapping samples) stridor (n = 17, 38%), obstructive sleep apnea (n = 14, 31%), central sleep apnea (n = 4, 9%), and ataxic breathing (n = 1). Except for three initial refusals and two yet untreated patients, fixed CPAP (n = 9), auto-adjusting CPAP (n = 8) and ASV (n = 2) were well-tolerated (limited leaks and good compliance) and successfully controlled stridor plus sleep apnea. Treated patients had survival times similar to those of patients without any sleep breathing disorder.ConclusionIn this small group, tailored management of stridor in MSA as an independent issue or combined with obstructive and central sleep apnea, yields a survival similar to survival in patients without sleep breathing disorders.



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AUTOMATED MECHANICAL PERIPHERAL STIMULATION IMPROVES GAIT PARAMETERS IN SUBJECTS WITH PARKINSON’S DISEASE AND FREEZING OF GAIT: A RANDOMIZED CLINICAL TRIAL

AbstractObjectiveThis study aimed to assess spatiotemporal gait parameters and lower limbs range of motion (ROM) in subjects with Parkinson's Disease (PD) and freezing of gait (FOG), treated with Automated Mechanical Peripheral Stimulation (AMPS) or AMPS SHAM (placebo).DesignThis randomized clinical trial included thirty subjects allocated into two groups: AMPS (15 subjects with PD) and AMPS SHAM (15 subjects with PD). Fourteen age-matched healthy subjects were also included as a REFERENCE group. Both PD groups received the treatment twice a week during 4 weeks. AMPS was applied using a commercial medical device (Gondola™) and consisted of mechanical pressure in four areas of feet. For AMPS SHAM group, a subliminal stimulus was delivered. Gait analyses were measured at PRE, POST 1st, POST 4th, and POST 8th sessions.ResultsWe did not find significant differences between AMPS and AMPS SHAM groups either for spatiotemporal gait parameters or for lower limbs ROM. However, within-group analysis showed that AMPS group significantly improved spatiotemporal gait parameters and hip rotation ROM throughout the treatment period. AMPS SHAM group did not show any improvement.ConclusionsAMPS therapy induces improvements in spatiotemporal parameters and hip rotation ROM of subjects with PD and FOG. Objective This study aimed to assess spatiotemporal gait parameters and lower limbs range of motion (ROM) in subjects with Parkinson's Disease (PD) and freezing of gait (FOG), treated with Automated Mechanical Peripheral Stimulation (AMPS) or AMPS SHAM (placebo). Design This randomized clinical trial included thirty subjects allocated into two groups: AMPS (15 subjects with PD) and AMPS SHAM (15 subjects with PD). Fourteen age-matched healthy subjects were also included as a REFERENCE group. Both PD groups received the treatment twice a week during 4 weeks. AMPS was applied using a commercial medical device (Gondola™) and consisted of mechanical pressure in four areas of feet. For AMPS SHAM group, a subliminal stimulus was delivered. Gait analyses were measured at PRE, POST 1st, POST 4th, and POST 8th sessions. Results We did not find significant differences between AMPS and AMPS SHAM groups either for spatiotemporal gait parameters or for lower limbs ROM. However, within-group analysis showed that AMPS group significantly improved spatiotemporal gait parameters and hip rotation ROM throughout the treatment period. AMPS SHAM group did not show any improvement. Conclusions AMPS therapy induces improvements in spatiotemporal parameters and hip rotation ROM of subjects with PD and FOG. Funding: A Research contract is active since November 2015 between the society Gondola Medical technology and Politecnico de Milano. Disclosures: The authors report no disclosures. Conflict of interests: None. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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MECHANICAL TRACTION FOR LUMBAR RADICULAR PAIN: SUPINE OR PRONE? A RANDOMIZED CONTROLLED TRIAL

ABSTRACTOBJECTIVETo compare the effects of mechanical lumbar traction either in the supine or prone position with conventional physical therapy(PT) in patients with chronic low back pain(LBP) and lumbosacral nerve root involvement in terms of disability, pain, and mobility.DESIGNParticipants(n=125) were randomly assingned to receive 15 sessions of PT with additional mechanical lumbar traction either in the supine position(supine traction group), or in the prone position(prone traction group), or only PT without traction(PT only group).Patients were assessed at baseline and at the end of the PT sessions in terms of disability, pain, and mobility.Disability was assessed using the modified Oswesty Disability Index(ODI); pain was assessed using a visual analogue scale (VAS); and lumbar mobility was assessed using the modified lumbar Schober test (mLST).RESULTS118 patients completed the trial.All groups improved significantly in the ODI, VAS, and mLST(P<.05 in the between-group analysis improvements of odi and vas were found significantly better prone traction group compared with pt only p=".031" .006 respectively position to other modalities resulted larger immediate terms pain disability results suggest that when using might be first-choice.further research is needed confirm benefits lumbar position. objective compare effects mechanical either supine or conventional physical therapy patients chronic low back lumbosacral nerve root involvement mobility. design participants randomly assingned receive sessions additional without assessed at baseline end mobility.disability was modified oswesty index a visual analogue scale mobility schober test completed trial.all groups improved mlst conclusion addition address correspondence to: meral bilgilisoy filiz antalya training hospital varlik mahallesi kazim karabekir cad. so turkey. e-mail: mbilgilisoy there no competing interest. funding received for our study. copyright wolters kluwer health inc. all rights reserved.>

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Intersection Syndrome Revisited: Let’s Talk Much More About It Using Ultrasound

No abstract available

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NIST launches challenge for first responder virtual reality display

They will award up to $125,000 for the top seven designs that create a concept for a first responder heads-up display

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Supportive properties of basement membrane layer of human amniotic membrane enable development of tissue engineering applications

Abstract

Human amniotic membrane (HAM) has been widely used as a natural scaffold in tissue engineering due to many of its unique biological properties such as providing growth factors, cytokines and tissue inhibitors of metalloproteinases. This study aimed at finding the most suitable and supportive layer of HAM as a delivery system for autologous or allogeneic cell transplantation. Three different layers of HAM were examined including basement membrane, epithelial and stromal layers. In order to prepare the basement membrane, de-epithelialization was performed using 0.5 M NaOH and its efficiency was investigated by histological stainings, DNA quantification, biomechanical testing and electron microscopy. Adipose-derived stromal cells (ASCs) and a human immortalized keratinocyte cell line (HaCaT) were seeded on the three different layers of HAM and cultured for 3 weeks. The potential of the three different layers of HAM to support the attachment and viability of cells were then monitored by histology, electron microscopy and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, mechanical strengths of the basement membrane were assessed before and after cell culture. The results indicated that the integrity of extra cellular matrix (ECM) components was preserved after de-epithelialization and resulted in producing an intact basement amniotic membrane (BAM). Moreover, all three layers of HAM could support the attachment and proliferation of cells with no visible cytotoxic effects. However, the growth and viability of both cell types on the BAM were significantly higher than the other two layers. We conclude that growth stimulating effectors of BAM and its increased mechanical strength after culturing of ASCs, besides lack of immunogenicity make it an ideal model for delivering allogeneic cells and tissue engineering applications.

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Correction to: Migraine Treatment: Current Acute Medications and Their Potential Mechanisms of Action

Abstract

This article was updated to correct an error in figure 1 introduced during the production process.

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Microbiome, Immunomodulation, and the Neuronal System

Abstract

Vertebrates harbor both symbiotic and pathogenic bacteria on the body and various mucosal surfaces. Of these surfaces, the intestine has the most diverse composition. This composition is dependent upon various environmental and genetic factors, with diet exerting the maximum influence. Significant roles of the intestinal bacteria are to stimulate the development of a competent mucosal immune system and to maintain tolerance within the intestine. One manner in which this is achieved is by the establishment of epithelial integrity by microbiota found in healthy individuals (healthy microbiota); however, in the case of a disrupted intestinal microbiome (dysbiosis), which can be caused by various conditions, the epithelial integrity is compromised. This decreased epithelial integrity can then lead to luminal products crossing the barrier, generating a systemic proinflammatory response. In addition to epithelial integrity, healthy intestinal commensals metabolize indigestible dietary substrates and produce short-chain fatty acids, which are bacterial metabolites that are essential for colonic health and regulating the function of the intestinal immune system. Intestinal commensals are also capable of producing neuroactive molecules and neurotransmitters that can affect the function of the vagus nerve. The observations that intestinal dysbiosis is associated with different diseases of the nervous system, suggests that cross-talk occurs amongst the gut, the nervous system, and the immune system.

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Validation and Psychometric Properties of the German Version of the SWAL-QOL

Abstract

The SWAL-QOL questionnaire is a common tool for evaluating patients' dysphagia-specific quality of life. A validated German version is not available. This study aimed to establish a German version of the SWAL-QOL (G-SWAL-QOL) using a standardized translation procedure and to systematically evaluate its psychometric properties. The original SWAL-QOL was translated into German following international translation guidelines. A pilot study (45 subjects) confirmed comprehensibility of the G-SWAL-QOL. A consecutive series of 158 subjects (103 patients with dysphagia; 55 healthy controls) was then recruited to assess validity and reliability of the G-SWAL-QOL. Construct validity was analyzed through a correlation analysis with both (i) the Anderson Dysphagia Inventory (ADI-D) and (ii) the Short Form 36 (SF-36). Internal consistency and test–retest reliability were evaluated to determine reliability. All questions of the G-SWAL-QOL were comprehensible, except one which was subsequently revised. Construct validity of the G-SWAL-QOL was demonstrated by moderate to high correlations with the ADI-D (Spearman's rho 0.36 – 0.88). The G-SWAL-QOL was able to differentiate between patients with dysphagia and healthy controls (p < 0.001) and was sensitive to disease severity measured by different food textures. Reliability of the G-SWAL-QOL was good to excellent for both internal consistency (Cronbach's α > 0.7 for all domains, except eating desire [α = 0.69]) and test–retest reliability (Spearman's rho ≥ 0.68 for all domains; ICC > 0.8 for all domains). The G-SWAL-QOL is a valid and reliable measuring tool for dysphagia-specific quality of life in German-speaking persons.

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Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases

by Anza B. Memon, Adil Javed, Christina Caon, Shitiz Srivastawa, Fen Bao, Evanthia Bernitsas, Jessica Chorostecki, Alexandros Tselis, Navid Seraji-Bozorgzad, Omar Khan

Background

B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND), such as neuromyelitis optica (NMO), multiple sclerosis (MS), and myasthenia gravis (MG). Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time.

Objective

The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer.

Methods

This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE), serious adverse events (SAE), and malignancies were observed.

Results

There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months) and 1 SAE was observed after 11 cycles (60 months) of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML) and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period.

Conclusions

This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

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Association studies of WD repeat domain 3 and chitobiosyldiphosphodolichol beta-mannosyltransferase genes with schizophrenia in a Japanese population

by Momoko Kobayashi, Daisuke Jitoku, Yoshimi Iwayama, Naoki Yamamoto, Tomoko Toyota, Katsuaki Suzuki, Mitsuru Kikuchi, Tasuku Hashimoto, Nobuhisa Kanahara, Akeo Kurumaji, Takeo Yoshikawa, Toru Nishikawa

Schizophrenia and schizophrenia-like symptoms induced by the dopamine agonists and N-methyl-D aspartate type glutamate receptor antagonists occur only after the adolescent period. Similarly, animal models of schizophrenia by these drugs are also induced after the critical period around postnatal week three. Based upon the development-dependent onsets of these psychotomimetic effects, by using a DNA microarray technique, we identified the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes as novel candidates for schizophrenia-related molecules, whose mRNAs were up-regulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor. WDR3 and other related proteins are the nuclear proteins presumably involved in various cellular activities, such as cell cycle progression, signal transduction, apoptosis, and gene regulation. ALG1 is presumed to be involved in the regulation of the protein N-glycosylation. To further elucidate the molecular pathophysiology of schizophrenia, we have evaluated the genetic association of WDR3 and ALG1 in schizophrenia. We examined 21 single nucleotide polymorphisms [SNPs; W1 (rs1812607)-W16 (rs6656360), A1 (rs8053916)-A10 (rs9673733)] from these genes using the Japanese case-control sample (1,808 schizophrenics and 2,170 matched controls). No significant genetic associations of these SNPs were identified. However, we detected a significant association of W4 (rs319471) in the female schizophrenics (allelic P = 0.003, genotypic P = 0.008). Based on a haplotype analysis, the observed haplotypes consisting of W4 (rs319471)–W5 (rs379058) also displayed a significant association in the female schizophrenics (P = 0.016). Even after correction for multiple testing, these associations remained significant. Our findings suggest that the WDR3 gene may likely be a sensitive factor in female patients with schizophrenia, and that modification of the WDR3 signaling pathway warrants further investigation as to the pathophysiology of schizophrenia.

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ShinyGPA: An interactive visualization toolkit for investigating pleiotropic architecture using GWAS datasets

by Emma Kortemeier, Paula S. Ramos, Kelly J. Hunt, Hang J. Kim, Gary Hardiman, Dongjun Chung

In spite of accumulating evidence suggesting that different complex traits share a common risk basis, namely pleiotropy, effective investigation of pleiotropic architecture still remains challenging. In order to address this challenge, we developed ShinyGPA, an interactive and dynamic visualization toolkit to investigate pleiotropic structure. ShinyGPA requires only the summary statistics from genome-wide association studies (GWAS), which reduces the burden on researchers using this tool. ShinyGPA allows users to effectively investigate genetic relationships among phenotypes using a flexible low-dimensional visualization and an intuitive user interface. In addition, ShinyGPA provides joint association mapping functionality that can facilitate biological understanding of the pleiotropic architecture. We analyzed GWAS summary statistics for 12 phenotypes using ShinyGPA and obtained visualization results and joint association mapping results that are well supported by the literature. The visualization produced by ShinyGPA can also be used as a hypothesis generating tool for relationships between phenotypes, which might also be used to improve the design of future genetic studies. ShinyGPA is currently available at http://ift.tt/2Eoj181.

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Ecological assessment of the marine ecosystems of Barbuda, West Indies: Using rapid scientific assessment to inform ocean zoning and fisheries management

by Benjamin Ruttenberg, Jennifer E. Caselle, Andrew J. Estep, Ayana Elizabeth Johnson, Kristen L. Marhaver, Lee J. Richter, Stuart A. Sandin, Mark J. A. Vermeij, Jennifer E. Smith, David Grenda, Abigail Cannon

To inform a community-based ocean zoning initiative, we conducted an intensive ecological assessment of the marine ecosystems of Barbuda, West Indies. We conducted 116 fish and 108 benthic surveys around the island, and measured the abundance and size structure of lobsters and conch at 52 and 35 sites, respectively. We found that both coral cover and fish biomass were similar to or lower than levels observed across the greater Caribbean; live coral cover and abundance of fishery target species, such as large snappers and groupers, was generally low. However, Barbuda lacks many of the high-relief forereef areas where similar work has been conducted in other Caribbean locations. The distribution of lobsters was patchy, making it difficult to quantify density at the island scale. However, the maximum size of lobsters was generally larger than in other locations in the Caribbean and similar to the maximum size reported 40 years ago. While the lobster population has clearly been heavily exploited, our data suggest that it is not as overexploited as in much of the rest of the Caribbean. Surveys of Barbuda's Codrington Lagoon revealed many juvenile lobsters, but none of legal size (95 mm carapace length), suggesting that the lagoon functions primarily as nursery habitat. Conch abundance and size on Barbuda were similar to that of other Caribbean islands. Our data suggest that many of the regional threats observed on other Caribbean islands are present on Barbuda, but some resources—particularly lobster and conch—may be less overexploited than on other Caribbean islands. Local management has the potential to provide sustainability for at least some of the island's marine resources. We show that a rapid, thorough ecological assessment can reveal clear conservation opportunities and facilitate rapid conservation action by providing the foundation for a community-driven policymaking process at the island scale.

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Risk assessment of the onset of Osgood–Schlatter disease using kinetic analysis of various motions in sports

by Gento Itoh, Hideyuki Ishii, Haruyasu Kato, Yasuharu Nagano, Hiroteru Hayashi, Hiroki Funasaki

Background

Some studies have listed motions that may cause Osgood-Schlatter disease, but none have quantitatively assessed the load on the tibial tubercle by such motions.

Purposes

To quantitatively identify the load on the tibial tubercle through a biomechanical approach using various motions that may cause Osgood-Schlatter disease, and to compare the load between different motions.

Methods

Eight healthy male subjects were included. They conducted 4 types of kicks with a soccer ball, 2 types of runs, 2 types of squats, 2 types of jump landings, 2 types of stops, 1 type of turn, and 1 type of cutting motion. The angular impulse was calculated for knee extension moments ≥1.0 Nm/kg, ≥1.5 Nm/kg, ≥2.0 Nm/kg, and ≥2.5 Nm/kg. After analysis of variance, the post-hoc test was used to perform pairwise comparisons between all groups.

Results/Conclusions

The motion with the highest mean angular impulse of knee extension moment ≥1.0 Nm/kg was the single-leg landing after a jump, and that with the second highest mean was the cutting motion. At ≥1.5 Nm/kg, ≥2.0 Nm/kg, and ≥2.5 Nm/kg, the cutting motion was the highest, followed by the jump with a single-leg landing. They have a large load, and are associated with a higher risk of developing Osgood-Schlatter disease. The mean angular impulse of the 2 types of runs was small at all the indicators.

Clinical relevance

Motions with a high risk of developing Osgood-Schlatter disease and low-risk motions can be assessed in further detail if future studies can quantify the load and number of repetitions that may cause Osgood-Schlatter disease while considering age and the development stage. Scheduled training regimens that balance load on the tibial tubercle with low-load motions after a training day of many load-intensive motions may prevent athletes from developing Osgood-Schlatter disease and increase their participation in sports.

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Biodegradative potential of fungal isolates from sacral ambient: In vitro study as risk assessment implication for the conservation of wall paintings

by Nikola Unković, Ivica Dimkić, Miloš Stupar, Slaviša Stanković, Jelena Vukojević, Milica Ljaljević Grbić

The principal purpose of the study was to evaluate in vitro the potential ability of fungal isolates obtained from the painted layer of frescoes and surrounding air to induce symptoms of fresco deterioration, associated with their growth and metabolism, so that the risk of such deterioration can be precisely assessed and appropriate conservation treatments formulated. Biodegradative properties of the tested microfungi were qualitatively characterized through the use of a set of special agar plates: CaCO₃ glucose agar (calcite dissolution), casein nutrient agar (casein hydrolysis), Czapek-Dox minimal medium (pigment secretion); and Czapek-Dox minimal broth (acid and alkali production). Most of the tested isolates (71.05%) demonstrated at least one of the degradative properties, with Penicillium bilaiae as the most potent, since it tested positive in all four. The remaining isolates (28.95%) showed no deterioration capabilities and were hence considered unlikely to partake in the complex process of fungal deterioration of murals via the tested mechanisms. The obtained results clearly indicate that utilization of fast and simple plate assays can provide insight into the biodegradative potential of deteriogenic fungi and allow for their separation from allochthonous transients, a prerequisite for precise assessment of the amount of risk posed by a thriving mycobiota to mural paintings.

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Consumption of alcohol and blood pressure: Results of the ELSA-Brasil study

by Nathália Miguel Teixeira Santana, José Geraldo Mill, Gustavo Velasquez-Melendez, Alexandra Dias Moreira, Sandhi Maria Barreto, Maria Carmen Viana, Maria del Carmen Bisi Molina

Background

Prevention and reduction of excessive use of alcohol represents damages to society in general. In turn, arterial hypertension is the main attributable risk factor premature life lost years and disability.

Objective

To investigate the relationship between alcohol consumption and high blood pressure in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methodology

A baseline data of total of 7,655 participants volunteers between 35 and 74 years of age, of both genders, in six educational and research institutions of three different regions of the country were interviewed between 2008–2010. Socioeconomic, haemodynamic, anthropometric and health data were collected in the research centers of ELSA-Brasil. The presence of high blood pressure was identified when the systolic blood pressure was ≥140 mm Hg and/or the diastolic was ≥90 mm Hg. Alcohol consumption was estimated and categorized regarding consumption and pattern of ingestion. The Student's t-test, chi-squared and logistic regression tests were used for analysis, including potential co-variables of the model, and a 5% significance level was adopted.

Results

A dose-response relation was observed for the consumption of alcohol (g/week) in systolic blood pressure and diastolic blood pressure. Alcohol consumption was associated with high blood pressure in men who reported moderate (OR = 1.69; _95%CI 1.35–2.11) and excessive (OR = 2.70; _95%CI 2.04–3.59) consumption. Women have nearly three times more chance of presenting elevated blood pressure when presenting excessive consumption (OR = 2.86, _95%CI 1.77–4.63), and binge drinkers who drink more than 2 to 3 times a month have approximately 70% more chance of presenting with elevated blood pressure, after adjusting for consumption of drinks with meals.

Conclusion

The consumption of alcohol beverages increases the odds of elevated blood pressure, especially among excessive drinkers. Therefore alcohol consumption needs a more robust regulation in view of its impact on population health.

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Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX

by Jennifer S. McDonald, Robert J. McDonald, Jacob B. Ekins, Anthony S. Tin, Sylvain Costes, Tamara M. Hudson, Dana J. Schroeder, Kevin Kallmes, Scott H. Kaufmann, Philip M. Young, Aiming Lu, Ramanathan Kadirvel, David F. Kallmes

Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR) exam. Sixty patients were enrolled (median age 55 years, 39 males). Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90), but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140). Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25%) increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure.

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Enhancement of lateral flow assay performance by electromagnetic relocation of reporter particles

by Maria João Jacinto, João R. C. Trabuco, Binh V. Vu, Gavin Garvey, Mohammad Khodadady, Ana M. Azevedo, Maria Raquel Aires-Barros, Long Chang, Katerina Kourentzi, Dmitri Litvinov, Richard C. Willson

Lateral flow assays (LFAs) are a widely-used point-of care diagnostic format, but suffer from limited analytical sensitivity, especially when read by eye. It has recently been reported that LFA performance can be improved by using magnetic reporter particles and an external magnetic field applied at the test line. The mechanism of sensitivity/performance enhancement was suggested to be concentration/retardation of reporter particles at the test line. Here we demonstrate an additional mechanism of particle relocation where reporter particles from the lower depths of the translucent LFA strip relocate to more-visible locations nearer to the top surface, producing a more visible signal. With a magnetic field we observed an improvement in sensitivity of human chorionic gonadotropin (hCG) detection from 1.25 ng/mL to 0.31 ng/mL. We also observed an increase of the color intensity per particle in test lines when the magnetic field was present.

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Comparison of eosin and fluorescein conjugates for the photoinitiation of cell-compatible polymer coatings

by Jacob L. Lilly, Anuhya Gottipati, Calvin F. Cahall, Mohamed Agoub, Brad J. Berron

Targeted photopolymerization is the basis for multiple diagnostic and cell encapsulation technologies. While eosin is used in conjunction with tertiary amines as a water-soluble photoinitiation system, eosin is not widely sold as a conjugate with antibodies and other targeting biomolecules. Here we evaluate the utility of fluorescein-labeled bioconjugates to photopolymerize targeted coatings on live cells. We show that although fluorescein conjugates absorb approximately 50% less light energy than eosin in matched photopolymerization experiments using a 530 nm LED lamp, appreciable polymer thicknesses can still be formed in cell compatible environments with fluorescein photosensitization. At low photoinitiator density, eosin allows more sensitive initiation of gelation. However at higher functionalization densities, the thickness of fluorescein polymer films begins to rival that of eosin. Commercial fluorescein-conjugated antibodies are also capable of generating conformal, protective coatings on mammalian cells with similar viability and encapsulation efficiency as eosin systems.

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Functional Two-Dimensional Coordination Polymeric Layer as a Charge Barrier in Li–S Batteries

ACS Nano

DOI: 10.1021/acsnano.7b08223

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Anatomy Monday: Nasolabial Fold

Off to a fun anatomy to start the new year off and it's been a while since I've shown a few more examples of this one. This one sometimes tricks a few people at first when trying to figure it out. This week is a soft tissue entity visible on both intraoral and extraoral radiographs. The […]

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Shocking News about Tinnitus Treatment

Precisely timed sound stimulation coupled with weak electrical pulses delivered to the neck or cheeks could bring relief from tinnitus. This is the potentially ground-breaking news from researchers at the University of Michigan. Let's start at the beginning, shall we?

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Glucocorticoids, Inflammation and Bone

Abstract

The current review on glucocorticoids (GCs), inflammation and bone is focused on three aspects: (1) the mutual effects between GCs, inflammation and bone in inflammatory rheumatic diseases, (2) current views on fracture risk assessment in patients using GCs and (3) non-pharmacological and pharmacological treatment to prevent fractures in GC-using patients with inflammatory rheumatic diseases. The use of GCs results in increased risk for fractures due to both direct and indirect negative effects of GCs on bone mass, and on bone and muscle strength. However, also the underlying inflammatory rheumatic disease is associated with the increased bone loss and fracture risk due to the chronic inflammation itself, and due to disability/immobility caused by active disease or joint destruction. The rapid and strong anti-inflammatory effect of GCs in patients with rheumatoid arthritis seems to balance the negative effects of GCs on bone in the early, active phase of the disease. Recently, an update of the American College of Rheumatology guidelines for prevention and treatment of GC-induced osteoporosis was published with renewed recommendations. To prevent fractures, general measures, including treatment of the underlying inflammatory disease adequately (even with GCs when indicated), a healthy lifestyle, including adequate calcium and vitamin D supplementation, and regular weight bearing exercises are important. In rheumatic patients with high fracture risk using GCs, especially when the cumulative dose is high and/or the underlying inflammatory disease is active, treatment with anti-osteoporotic drugs, usually an oral bisphosphonate, is indicated.

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Driver education: Enhancing knowledge of sleep, fatigue and risky behaviour to improve decision making in young drivers

Publication date: March 2018
Source:Accident Analysis & Prevention, Volume 112
Author(s): Pasquale K. Alvaro, Nicole M. Burnett, Gerard A. Kennedy, William Yu Xun Min, Marcus McMahon, Maree Barnes, Melinda Jackson, Mark E. Howard
This study assessed the impact of an education program on knowledge of sleepiness and driving behaviour in young adult drivers and their performance and behaviour during simulated night driving.Thirty-four participants (18–26 years old) were randomized to receive either a four-week education program about sleep and driving or a control condition. A series of questionnaires were administered to assess knowledge of factors affecting sleep and driving before and after the four-week education program. Participants also completed a two hour driving simulator task at 1am after 17 h of extended wakefulness to assess the impact on driving behaviour.There was an increase in circadian rhythm knowledge in the intervention group following the education program. Self-reported risky behaviour increased in the control group with no changes in other aspects of sleep knowledge. There were no significant differences in proportion of intervention and control participants who had microsleeps (p ≤ .096), stopped driving due to sleepiness (p = .107), recorded objective episodes of drowsiness (p = .455), and crashed (p = .761), although there was a trend towards more control participants having microsleeps and stopping driving. Those in the intervention group reported higher subjective sleepiness at the end of the drive [M = 6.25, SD = 3.83, t(31) = 2.15, p = .05] and were more likely to indicate that they would stop driving [M = 3.08, SD = 1.16, t(31) = 2.24, p = .04].The education program improved some aspects of driver knowledge about sleep and safety. The results also suggested that the education program lead to an increased awareness of sleepiness. Education about sleep and driving could reduce the risk of drowsy driving and associated road trauma in young drivers, but requires evaluation in a broader sample with assessment of real world driving outcomes.



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Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice

ACS Nano

DOI: 10.1021/acsnano.7b04321

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Graphene-Based Standalone Solar Energy Converter for Water Desalination and Purification

ACS Nano

DOI: 10.1021/acsnano.7b08196

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Photocatalytically Active Superstructures of Quantum Dots and Iron Porphyrins for Reduction of CO2 to CO in Water

ACS Nano

DOI: 10.1021/acsnano.7b07377

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Toxins, Vol. 10, Pages 33: Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

Toxins, Vol. 10, Pages 33: Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

Toxins doi: 10.3390/toxins10010033

Authors: Raymond Vanholder Anneleen Pletinck Eva Schepers Griet Glorieux

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β2-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.

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Hydrodynamic Renal Pelvis Injection for Non-viral Expression of Proteins in the Kidney

This protocol describes a method to inject plasmid DNA into the mouse kidney via the renal pelvis to produce transgene expression specifically in the kidney.

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Explanations for the high potency of HPV prophylactic vaccines

Publication date: Available online 8 January 2018
Source:Vaccine
Author(s): John Schiller, Doug Lowy
HPV L1 virus-like particle (VLP) vaccines administered in a prime/boost series of three injections over six months have demonstrated remarkable prophylactic efficacy in clinical trials and effectiveness in national immunization programs with high rates of coverage. There is mounting evidence that the vaccines have similar efficacy and effectiveness even when administered in a single dose. The unexpected potency of one dose of these VLP vaccines may largely be attributed to structural features of the particles, which lead to the efficient generation of long-lived antigen-specific antibody-producing cells and unique features of the virus life cycle that make the HPV virions highly susceptible to antibody-mediated inhibition of infection.



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Expertos dan la alarma | Más mujeres en EE. UU. son obesas antes del embarazo

"Lamentablemente, muchas de esas mujeres aumentarán demasiado de peso durante el embarazo, y no perderán el peso después"

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Warum werden Wale gejagt?

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Organizing a Global Idiom. Esperanto, Ido and the World Auxiliary Language Movement before the First World War

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Influence of antrum size on gastric emptying and weight-loss outcomes after laparoscopic sleeve gastrectomy (preliminary analysis of a randomized trial)

Abstract

Background

Laparoscopic sleeve gastrectomy (LSG) has increased in popularity in recent years as a definitive bariatric procedure. Despite its growing popularity worldwide, the surgical technique is not well standardized. There is a lack of evidence on the matter of the antrum size and its relation to gastric emptying and weight-loss outcomes. The aim of the study is to evaluate the influence of antrum size over gastric emptying and weight-loss outcomes.

Methods

Twenty-five patients were prospectively randomized according to the distance between the first firing and the pylorus: AR group (antrum resection—2 cm from the pylorus) and AP group (antrum preservation—5 cm from the pylorus). Gastric emptying (%GE) was evaluated by a gastric emptying scintigraphy before surgery, 2 months and 1 year after LSG. Antrum volume was measured using a MultiSlice CT Scan performed 2 months and 1 year after surgery. The percent of excess weight loss (%EWL) was calculated after 1 year follow-up.

Results

At 2 months after LSG the mean %GE was 69.7 ± 18 in the AR group and 72.8 ± 20 in the AP group (p = 0.69). At 1 year it was 66.5 ± 21 and 74.2 ± 16 in the AR and AP groups, respectively (p = 0.30). A significant accelerated gastric emptying was observed at 2 months (p = 0.025) and at 1 year (p = 0.013) in the AP group. Meanwhile in the AR group this increase was not significant (p = 0.12 at 2 months and p = 0.21 at 1 year). Differences regarding the %EWL between groups were no statistically significant (p = 0.74).

Conclusions

After LSG there is a global tendency to an accelerated gastric emptying, although only significant in the antrum preservation group; however, no differences were observed regarding the %EWL between groups after 1 year follow-up.

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Nogo-A interacts with TrkA to alter nerve growth factor signaling in Nogo-A-overexpressing PC12 cells

Publication date: Available online 8 January 2018
Source:Cellular Signalling
Author(s): Robert G. Farrer, Gwendolyn L. Kartje
The Nogo-A protein, originally discovered as a potent myelin-associated inhibitor of neurite outgrowth, is also expressed by certain neurons, especially during development and after injury, but its role in neuronal function is not completely known. In this report, we overexpressed Nogo-A in PC12 cells to use as a model to identify potential neuronal signaling pathways affected by endogenously expressed Nogo-A. Unexpectedly, our results show that viability of Nogo-A-overexpressing cells was reduced progressively due to apoptotic cell death following NGF treatment, but only after 24 h. Inhibitors of neutral sphigomyelinase prevented this loss of viability, suggesting that NGF induced the activation of a ceramide-dependent cell death pathway. Nogo-A over-expression also changed NGF-induced phosphorylation of TrkA at tyrosines 490 and 674/675 from sustained to transient, and prevented the regulated intramembrane proteolysis of p75^NTR, indicating that Nogo-A was altering the function of the two neurotrophin receptors. Co-immunoprecipitation studies revealed that there was a physical association between TrkA and Nogo-A which appeared to be dependent on interactions in the Nogo-A-specific region of the protein. Taken together, our results indicate that Nogo-A influences NGF-mediated mechanisms involving the activation of TrkA and its interaction with p75^NTR.



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Mesenteric Panniculitis—First Case Series After Bariatric Surgery

Abstract

Mesenteric panniculitis is an uncommon pathology, of poorly understood etiology, characterized by progressive inflammation and fibrosis of the small bowel mesentery. This disease has been reported usually after other abdominal surgeries. We present two cases of young male patients who underwent laparoscopic sleeve gastrectomy and developed abdominal symptoms within 45–60 days of surgery. Both were investigated for known post-bariatric complications. While first patient presented (5 months later) at an irreversible stage and died within 8–9 months of primary surgery, in second patient, the disease process could be reversed through early intervention, diagnosis, treatment, and compliance. Mesenteric panniculitis is a rapidly progressive entity, which can be adequately treated by early identification and long-term immune-suppressive therapy.

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Screening protocol for dysphagia in adults: comparison with videofluoroscopic findings

OBJECTIVES: To compare the videofluoroscopic findings of patients with suspected oropharyngeal dysphagia with the results of a clinical screening protocol. METHODS: A retrospective observational cohort study was conducted on all consecutive patients with suspected oropharyngeal dysphagia between March 2015 and February 2016 who were assigned to receive a videofluoroscopic assessment of swallowing. All patients were first submitted to videofluoroscopy and then to the clinical assessment of swallowing. The clinical assessment was performed within the first 24 hours after videofluoroscopy. The videofluoroscopy results were analyzed regarding penetration/aspiration using an 8-point multidimensional perceptual scale. The accuracy of the clinical protocol was analyzed using the sensitivity, specificity, likelihood ratios and predictive values. RESULTS: The selected sample consisted of 50 patients. The clinical protocol presented a sensitivity of 50% and specificity of 95%, with an accuracy of 88%. "Cough" and "wet-hoarse" vocal quality after/during swallowing were clinical indicators that appeared to correctly identify the presence of penetration/aspiration risk. CONCLUSION: The clinical protocol used in the present study is a simple, rapid and reliable clinical assessment. Despite the absence of a completely satisfactory result, especially in terms of the sensitivity and positive predictive values, we suggest that lower rates of pneumonia can be achieved using a formal dysphagia screening method.

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Serum 25-hydroxyvitamin D levels in patients with Granulomatosis with Polyangiitis: association with respiratory infection

OBJECTIVES: To determine the possible association of serum 25-hydroxyvitamin D (25OHD) levels with disease activity and respiratory infection in granulomatosis with polyangiitis patients during two different periods: winter/spring and summer/autumn. METHODS: Thirty-two granulomatosis with polyangiitis patients were evaluated in the winter/spring, and the same patients (except 5) were evaluated in summer/autumn (n=27). The 25OHD levels were measured by radioimmunoassay. Disease activity was assessed by the Birmingham Vasculitis Activity Score Modified for Wegener's Granulomatosis (BVAS/WG) and antineutrophil cytoplasmic antibody (ANCA) positivity. Respiratory infection was defined according the Centers for Disease Control and Prevention criteria. RESULTS: 25OHD levels were lower among patients in winter/spring than in summer/autumn (32.31±13.10 vs. 38.98±10.97 ng/mL, p=0.04). Seven patients met the criteria for respiratory infection: 5 in winter/spring and 2 in summer/autumn. Patients with respiratory infection presented lower 25OHD levels than those without infection (25.15±11.70 vs. 36.73±12.08 ng/mL, p=0.02). A higher frequency of low vitamin D levels (25OHD<20 ng/mL) was observed in patients with respiratory infection (37.5% vs. 7.8, p=0.04). Serum 25OHD levels were comparable between patients with (BVAS/WG≥1 plus positive ANCA) and without disease activity (BVAS/WG=0 plus negative ANCA) (35.40±11.48 vs. 35.34±13.13 ng/mL, p=0.98). CONCLUSIONS: Lower 25OHD levels were associated with respiratory infection but not disease activity in granulomatosis with polyangiitis patients. Our data suggest that hypovitaminosis D could be an important risk factor for respiratory infection in granulomatosis with polyangiitis patients.

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A new low-cost negative-pressure wound therapy versus a commercially available therapy device widely used to treat complex traumatic injuries: a prospective, randomized, non-inferiority trial

OBJECTIVES: Negative-pressure wound therapy has been widely adopted to reduce the complexity of treating a broad range of acute and chronic wounds. However, its cost is high. The objective of this study was to evaluate the following two different methods of negative-pressure wound therapy in terms of healing time: a low-cost method of negative-pressure wound therapy (a pressure stabilizer device connected to a hospital wall-vacuum system with a gauze-sealed dressing, USP) and the standard of care (vacuum-assisted closure, VAC). METHODS: This is a randomized, controlled, non-inferiority, unblinded trial. Patients admitted with complex injuries to a trauma center in a public referral hospital who were indicated for orthopedic surgery were randomized to a USP or VAC group. The primary outcome was the time required to achieve a "ready for surgery condition", which was defined as a wound bed with healthy granulation tissue and without necrosis or purulent secretion. Wound bed area contraction, granulation tissue growth and the direct costs of the dressings were secondary outcomes. RESULTS: Variation in area and granulation tissue growth were essentially the same between the systems, and healing time was equal between the groups (p=0.379). In both systems, serial debridement increased wound area (p=0.934), and granulation tissue was also increased (p=0.408). The mean treatment cost was US$ 15.15 in the USP group and US$ 872.59 in the VAC group. CONCLUSIONS: For treating complex traumatic injuries, USP was non-inferior to and less expensive than VAC.

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Depression and adherence to antiretroviral treatment in HIV-positive men in São Paulo, the largest city in South America: Social and psychological implications

OBJECTIVES: The aim of the present study was to investigate the prevalence of depression and adherence to antiretroviral treatment in two groups of individuals: men who have sex with men (MSM) and men who have sex with women (MSW). METHODS: Two hundred and sixteen participants (MSM=116; MSW=100) who visited the Clinics Hospital of the School of the Medicine of the University of São Paulo completed two independent surveys (the BECK Depression Inventory and an adherence self-declared questionnaire) to evaluate their depression status and adherence to antiretroviral treatment, respectively. RESULTS: The study highlighted a positive relationship between depression and low adherence to Highly Active Antiretroviral Therapy in these patients regardless of age and sexual orientation. In addition, MSM subjects were two times more prone than MSW subjects to develop depression symptoms. White or mixed race men showed 7.6 times greater adherence to treatment than black men. The probability of complete adherence to treatment was 3.8 times higher in non-depressed subjects than in depressed subjects regardless of their ethnicity. The chance of developing depression was 4.17 times higher for an individual with non-adherent behavior than for an adherent individual. CONCLUSIONS: Individuals with low adherence rates have proportionally higher depression rates. Depressed men tend to show less adherence to treatment. Black but not mixed race or white men show less adherence to Highly Active Antiretroviral Therapy and have a greater chance of developing depression, which directly interferes with adherence. The chances of developing depression are four times greater for a patient with non-adherent behavior than for a patient with adherent behavior.

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Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline

OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to develop a predictive model to estimate the probability of microcirculatory recruitment in patients with septic shock. METHODS: This prospective interventional study included patients with septic shock receiving noradrenaline for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour. Hemodynamic measurements, including sidestream dark-field imaging, were obtained immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1 hour after vasopressin withdrawal. We defined patients with more than a 10% increase in total vascular density and perfused vascular density as responders. ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and nine (50%) showed improved microcirculation after infusion of vasopressin. The noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was higher both at baseline and during vasopressin infusion in the responders than in the non-responders. The strongest predictor for a favorable microcirculatory response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0; p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min, the probability that microcirculatory perfusion would be improved with vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients with septic shock for no longer than 48 h, administration of vasopressin is likely to result in an improvement in microcirculation when the baseline noradrenaline dose is higher than 0.38 mcg/kg/min.

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Characteristics and Outcomes of Intensive Care Unit Survivors: Experience of a Multidisciplinary Outpatient Clinic in a Teaching Hospital

OBJECTIVES: To describe the experience of an outpatient clinic with the multidisciplinary evaluation of intensive care unit survivors and to analyze their social, psychological, and physical characteristics in a low-income population and a developing country. METHODS: Retrospective cohort study. Adult survivors from a general intensive care unit were evaluated three months after discharge in a post-intensive care unit outpatient multidisciplinary clinic over a period of 6 years (2008-2014) in a University Hospital in southern Brazil. RESULTS: A total of 688 out of 1945 intensive care unit survivors received care at the clinic. Of these, 45.2% had psychological disorders (particularly depression), 49.0% had respiratory impairments (abnormal spirometry), and 24.6% had moderate to intense dyspnea during daily life activities. Patients experienced weight loss during hospitalization (mean=11.7%) but good recovery after discharge (mean gain=9.1%), and 94.6% were receiving nutrition orally. One-third of patients showed a reduction of peripheral muscular strength, and 5.7% had moderate to severe tetraparesis or tetraplegia. There was a significant impairment in quality of life (SF-36), particularly in the physical and emotional aspects and in functional capacity. The economic impacts on the affected families, which were mostly low-income families, were considerable. Most patients did not have full access to rehabilitation services, even though half of the families were receiving financial support from the government. CONCLUSIONS: A significant number of intensive care unit survivors evaluated 3 months after discharge had psychological, respiratory, motor, and socioeconomic problems; these findings highlight that strategies aimed to assist critically ill patients should be extended to the post-hospitalization period and that this problem is particularly important in low-income populations.

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Evaluation of the efficacy and safety of endovascular management for transplant renal artery stenosis

OBJECTIVES: To evaluate the safety and efficacy of endovascular intervention with angioplasty and stent placement in patients with transplant renal artery stenosis. METHODS: All patients diagnosed with transplant renal artery stenosis and graft dysfunction or resistant systemic hypertension who underwent endovascular treatment with stenting from February 2011 to April 2016 were included in this study. The primary endpoint was clinical success, and the secondary endpoints were technical success, complication rate and stent patency. RESULTS: Twenty-four patients with transplant renal artery stenosis underwent endovascular treatment, and three of them required reinterventions, resulting in a total of 27 procedures. The clinical success rate was 100%. All graft dysfunction patients showed decreased serum creatinine levels and improved estimated glomerular filtration rates and creatinine levels. Patients with high blood pressure also showed improved control of systemic blood pressure and decreased use of antihypertensive drugs. The technical success rate of the procedure was 97%. Primary patency and assisted primary patency rates at one year were 90.5% and 100%, respectively. The mean follow-up time of patients was 794.04 days after angioplasty. CONCLUSION: Angioplasty with stent placement for the treatment of transplant renal artery stenosis is a safe and effective technique with good results in both the short and long term.

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EphB3 signaling induces cortical endothelial cell death and disrupts the blood–brain barrier after traumatic brain injury

EphB3 signaling induces cortical endothelial cell death and disrupts the blood–brain barrier after traumatic brain injury

EphB3 signaling induces cortical endothelial cell death and disrupts the blood–brain barrier after traumatic brain injury, Published online: 08 January 2018; doi:10.1038/s41419-017-0016-5

EphB3 signaling induces cortical endothelial cell death and disrupts the blood–brain barrier after traumatic brain injury

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Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior

Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior

Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior, Published online: 08 January 2018; doi:10.1038/s41419-017-0019-2

Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior

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Predictors of unknown cancer in patients with ischemic stroke

Abstract

Stroke is the second most frequent neurologic finding in postmortem studies of cancer patients. It has also been described as the first expression of an occult cancer. We have studied patients diagnosed with cancer after an ischemic stroke (IS) and we analyze differences with non-tumor patients. Single cohort longitudinal retrospective study of patients admitted to our center with IS diagnosis from 1 January 2012 to 12 December 2014. All patients were followed for 18 months. Patients with transient ischemic infarction or cerebral hemorrhage, active cancer or in the last 5 years, inability to follow-up or absence of complete complementary study (holter-EKG, echocardiogram, and dupplex/angiography-CT) were excluded. Demographic, clinical, analytical and prognostic characteristics were compared between both subgroups. From a total of 381 IS patients with no history of cancer, 29 (7.61%) were diagnosed with cancer. The mean time from stroke onset to cancer diagnosis was 6 months. The most frequent location was colon (24%). 35% were diagnosed in a metastatic stage. Older age (p = 0.003), previous cancer (p = 0.042), chronic kidney disease (CKD) (p = 0.006) and lower hemoglobin (p = 0.004) and fibrinogen (p = 0.019) values were predictors of occult neoplasm. No differences were found in other biochemical or epidemiological parameters, prognosis, etiology or clinical manifestations of the IS. In our study, older age, CKD, previous cancer and hemoglobin and fibrinogen values were related to the diagnosis of cancer after IS. More studies are needed to determine which patients could benefit from a larger study on admission that might allow an earlier diagnosis of the underlying neoplasm.

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Studying and modifying brain function with non-invasive brain stimulation

Studying and modifying brain function with non-invasive brain stimulation

Studying and modifying brain function with non-invasive brain stimulation, Published online: 08 January 2018; doi:10.1038/s41593-017-0054-4

Polanía, Nitsche and Ruff summarize the state of non-invasive brain stimulation research in humans, discuss some current debates about properties and limitations of these methods, and give recommendations for how these challenges may be addressed.

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Simple integration of fast excitation and offset, delayed inhibition computes directional selectivity in Drosophila

Simple integration of fast excitation and offset, delayed inhibition computes directional selectivity in Drosophila

Simple integration of fast excitation and offset, delayed inhibition computes directional selectivity in <i>Drosophila</i> , Published online: 08 January 2018; doi:10.1038/s41593-017-0046-4

In the Drosophila visual system, T4 is the first cell type in the ON pathway to exhibit directionally selective signals. This directional selectivity originates from simple integration of spatially offset fast excitatory and slow inhibitory inputs.

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Hexadirectional coding of visual space in human entorhinal cortex

Hexadirectional coding of visual space in human entorhinal cortex

Hexadirectional coding of visual space in human entorhinal cortex, Published online: 08 January 2018; doi:10.1038/s41593-017-0050-8

fMRI activity in human entorhinal cortex is modulated by eye-movement direction with 60° periodicity, implicating a grid cell-like code in mapping visual space. This suggests a role for entorhinal grid coding in cognition beyond spatial navigation.

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TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD

TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD

TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD, Published online: 08 January 2018; doi:10.1038/s41593-017-0047-3

Pathological TDP-43 protein aggregates are a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43 pathology alters the morphology of nuclear pore complexes and cause deficits in nucleocytoplasmic transport.

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Human entorhinal cortex represents visual space using a boundary-anchored grid

Human entorhinal cortex represents visual space using a boundary-anchored grid

Human entorhinal cortex represents visual space using a boundary-anchored grid, Published online: 08 January 2018; doi:10.1038/s41593-017-0049-1

The authors show that human entorhinal cortex supports a grid cell-like representation of visual space. This visual grid pattern is stably anchored to the external visual world in a fashion analogous to rodent grid representations of navigable space.

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Calibration of raw accelerometer data to measure physical activity: A systematic review

Publication date: March 2018
Source:Gait & Posture, Volume 61
Author(s): Márcio de Almeida Mendes, Inácio C.M. da Silva, Virgílio V. Ramires, Felipe F. Reichert, Rafaela C. Martins, Elaine Tomasi
Most of calibration studies based on accelerometry were developed using count-based analyses. In contrast, calibration studies based on raw acceleration signals are relatively recent and their evidences are incipient. The aim of the current study was to systematically review the literature in order to summarize methodological characteristics and results from raw data calibration studies. The review was conducted up to May 2017 using four databases: PubMed, Scopus, SPORTDiscus and Web of Science. Methodological quality of the included studies was evaluated using the Landis and Koch's guidelines. Initially, 1669 titles were identified and, after assessing titles, abstracts and full-articles, 20 studies were included. All studies were conducted in high-income countries, most of them with relatively small samples and specific population groups. Physical activity protocols were different among studies and the indirect calorimetry was the criterion measure mostly used. High mean values of sensitivity, specificity and accuracy from the intensity thresholds of cut-point-based studies were observed (93.7%, 91.9% and 95.8%, respectively). The most frequent statistical approach applied was machine learning-based modelling, in which the mean coefficient of determination was 0.70 to predict physical activity energy expenditure. Regarding the recognition of physical activity types, the mean values of accuracy for sedentary, household and locomotive activities were 82.9%, 55.4% and 89.7%, respectively. In conclusion, considering the construct of physical activity that each approach assesses, linear regression, machine-learning and cut-point-based approaches presented promising validity parameters.



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A prospective longitudinal study of Pasireotide in Nelson’s syndrome

Abstract

Purpose

Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome.

Methods

Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300–600 μg s.c. twice-daily; (3) 6 months pasireotide long-acting-release (LAR) 40–60 mg monthly.

Results

Seven patients had s.c. treatment and 5 proceeded to LAR treatment. There was a significant reduction in morning plasma ACTH during treatment (mean ± SD; 1823 ± 1286 ng/l vs. 888.0 ± 812.8 ng/l during the s.c. phase vs. 829.0 ± 1171 ng/l during the LAR phase, p < 0.0001). Analysis of ACTH levels using a random intercept linear mixed-random effects longitudinal model showed that ACTH (before the morning dose of glucocorticoids) declined significantly by 26.1 ng/l per week during the 28-week of treatment (95% CI − 45.2 to − 7.1, p < 0.01). An acute response to a test dose predicted outcome in 4/5 patients. Overall, there was no significant change in tumor volumes (1.4 ± 0.9 vs. 1.3 ± 1.0, p = 0.86). Four patients withdrew during the study. Hyperglycemia occurred in 6 patients.

Conclusions

Pasireotide lowers plasma ACTH levels in patients with Nelson's syndrome. A longer period of treatment may be needed to assess the effects of pasireotide on tumor volume.

Trial registration: Clinical Trials.gov ID, NCT01617733

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Radical-mediated formal C(sp2)-H functionalization of aldehyde-derived N,N-dialkylhydrazones

Recent advances in formal C(sp2)-H functionalization of aldehyde-derived N,N-dialkylhydrazones (substitution at azomethine carbon atom) are highlighted with a focus on radical-mediated processes that open up new opportunities for C-C bond formation such as alkylation reactions using hypervalent iodonium reagents or polyhaloalkanes, as well as for carbon-heteroatom bond formation (C-N, C-P). Cascade sequences based on these reactions, and leading to (hetero)cyclic frameworks, are also discussed.

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The impact of rural residence and HIV infection on poor tuberculosis treatment outcomes in a large urban hospital: a retrospective cohort analysis

Abstract

Background

Successful tuberculosis (TB) treatment is essential to effective TB control. TB-HIV coinfection, social determinants and access to services influenced by rural residence can affect treatment outcome. We examined the separate and joint effects of rural residence and HIV infection on poor treatment outcome among patients enrolled in a large TB treatment centre in Kano, Nigeria.

Methods

We retrospectively analysed a cohort of patients with TB enrolled in a large urban TB clinic in northern Nigeria, from January 2010 to December 2014. Poor treatment outcome was defined as death, default or treatment failure. We used Poisson regression to model rates and determine the relative risks (and 95% confidence intervals, CI) of poor treatment outcomes.

Results

Among 1381 patients included in the analysis, 28.4% were rural residents; 39.8% were HIV-positive; and 46.1% had a poor treatment outcome. Approximately 65 and 38% of rural and urban residents, respectively, had a poor treatment outcome. Rural residents had 2.74 times (95% CI: 2.27–3.29) the risk of having a poor treatment outcome compared to urban residents. HIV-positive patients had 1.4 times (95% CI: 1.16–1.69) the risk of poor treatment outcome compared to HIV-negative patients. The proportion of poor treatment outcome attributable to rural residence (population attributable fraction, PAF) was 25.6%. The PAF for HIV infection was 11.9%. The effect of rural residence on poor treatment outcome among HIV-negative patients (aRR:4.07; 95%CI:3.15–5.25) was more than twice that among HIV-positive patients (aRR:1.99; 95%CI:1.49–2.64).

Conclusion

Rural residents attending a large Nigerian TB clinic are at increased risk of having poor treatment outcomes, and this risk is amplified among those that are HIV-negative. Our findings indicate that rural coverage of HIV services may be better than TB services. These findings highlight the importance of expanding coverage of TB services to ensure prompt diagnosis and commencement of treatment, especially among rural-dwellers in resource-limited settings.

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Street-level workers’ inadequate knowledge and application of exemption policies in Burkina Faso jeopardize the achievement of universal health coverage: evidence from a cross-sectional survey

Abstract

Background

Street-level workers play a key role in public health policies in Africa, as they are often the ones to ensure their implementation. In Burkina Faso, the State formulated two different user-fee exemption policies for indigents, one for deliveries (2007), and one for primary healthcare (2009). The objective of this study was to measure and understand the determinants of street-level workers' knowledge and application of these exemption measures.

Methods

We used cross-sectional data collected between October 2013 and March 2014. The survey targeted 1521 health workers distributed in 498 first-line centres, 18 district hospitals, 5 regional hospitals, and 11 private or other facilities across 24 districts. We used four different random effects models to identify factors associated with knowledge and application of each of the above-mentioned exemption policies.

Results

Only 9.2% of workers surveyed knew of the directive exempting the worst-off, and only 5% implemented it. Knowledge and application of the delivery exemption were higher, with 27% of all health workers being aware of the delivery exemption directive and 24.2% applying it. Mobile health workers were found to be consistently more likely to apply both exemptions. Health workers who were facility heads were significantly more likely to know about the indigent exemption for primary health care and to apply it. Health workers in districts with higher proportions of very poor people were significantly more likely to know about and apply the delivery exemption. Nearly 60% of respondents indicated either 5% or 10% as the percentage of people they would deem adequate to target for exemption.

Conclusion

This quantitative study confirmed earlier qualitative results on the importance of training and informing health workers and monitoring the measures targeting equity, to ensure compliance with government directives. The local context (e.g., hierarchy, health system, interventions) and the ideas that street-level workers have about the policy instruments can influence their effective implementation. Methods for remunerating health workers and health centres also need to be adapted to ensure equity measures are applied to achieve universal healthcare.

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iTRAQ-based proteomic analysis to identify the molecular mechanism of Zhibai Dihuang Granule in the Yin-deficiency-heat syndrome rats

Abstract

Background

Zhibai Dihuang Granule (ZDG) is a traditional Chinese medicine which has been used to treat Yin-deficiency-heat (YDH) syndrome for thousands of years in China. However, little work has been conducted to explore the molecular mechanism of ZDG in YDH syndrome, and the processes of YDH syndrome prevention and treatment have been developed slowly. The present study was aimed to explore the therapeutic mechanism of ZDG on YDH syndrome.

Methods

The YDH syndrome rats were induced by hot Chinese herbs, then treated by ZDG orally for 1 week. Body weight was measured every 2 days. After sacrifice, blood samples were collected and the thymus, adrenal glands, spleen, and liver were immediately removed and weighed. iTRAQ-based proteomics approach was applied to explore the serum protein alterations with the treatment of ZDG, and to investigate the underlying mechanism of ZDG in treating YDH syndrome.

Results

The body weights of YDH syndrome rats were significantly decreased compared with control group, and increased in ZDG treated rats. The relative weights of thymus in YDH syndrome rats were increased compared with the control rats, and significantly decreased in after ZDG treatment. In the proteomic analyses, seventy-one proteins were differentially expressed in the YDH syndrome group and the ZDG treated group, including 10 up-regulated and 61 down-regulated proteins. Gene ontology analysis revealed that the differentially expressed proteins were mostly related to immune response, and pathway enrichment analysis showed that these proteins were enriched in coagulation and complement cascades. Enzyme-linked immunosorbent assay was performed to detect the protein levels in coagulation and complement cascades, and the results showed that complement component 5 levels were significantly increased, while fibrinogen gamma chain levels were significantly decreased in the ZDG treated group.

Conclusions

We found that ZDG treatment could lead to proteins alteration in immune response, especially in coagulation and complement cascades. ZDG can up-regulate the proteins in the complement cascade to eliminate pathogens, and down-regulate the proteins in the coagulation cascade to suppress inflammation. Our study provides experimental basis to understand the therapeutic mechanism of ZDG and revealed that ZDG can regulate coagulation and complement cascades in treating YDH syndrome.

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Nichtinvasive Beatmung zur Behandlung akuter respiratorischer Insuffizienz

Zusammenfassung

Die nichtinvasive Beatmung stellt ein Beatmungsverfahren dar, mit dem sich beatmungsassoziierte Komplikationen einer invasiven Beatmung vermindern lassen. Dadurch kann insbesondere das Outcome von Patienten mit akuter hyperkapnischer respiratorischer Insuffizienz oder einer hypoxischen respiratorischen Insuffizienz bei kardialem Lungenödem verbessert werden. Entscheidend für den erfolgreichen und sicheren Einsatz der nichtinvasiven Beatmung ist die richtige praktische Durchführung.

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Navigating climate-related challenges on working lands: a special issue by the USDA Climate Hubs and their partners

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Endosulfan Plant Uptake Suppression Effect on Char Amendment in Oriental Radish

Abstract

Persistent organic pollutants (POPs) immobilization in farm land is an important issue to solve the residue in crop, and char has been considered for the remediation. In here, three commercially available chars like powdered oak char (POC), granulated oak char (GOC), and rice husk char (RHC) including powdered activated carbon (PAC) were investigated for their potential to adsorb and immobilize endosulfan in the soil. The maximum adsorption capacities (mg g⁻¹) of the applied chars as POC, GOC, and RHC were 714.8, 322.6, and 181.8, respectively, and the capacity of POC was similar with PAC (713.8). In addition, the pore volume (0.138 cm³ g⁻¹) and the surface area (270.3 m² g⁻¹) of POC were over 3-fold higher than GOC and RHC. The bioconcentration factor (BCF) reducing effect of α-, β-endosulfan, and endosulfan sulfate in oriental radish (Raphanus sativus var. sativus) was investigated by amendment of three commercially available chars to the contaminated soils. The BCF of total endosulfan was 0.025 in the radish root. POC treatments effectively suppressed the endosulfan uptake (BCF 0.002). However, GOC and RHC showed little BCF reducing effect of endosulfan in radish.

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