Medicine by Alexandros G. Sfakianakis: December 2017

Wednesday, December 13, 2017

Das Sprechen im Rundfunk als interaktive Montage verschiedener Ressourcen

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Longitudinal assessment of rabbit renal fibrosis induced by unilateral ureteral obstruction using two-dimensional susceptibility weighted imaging

BACKGROUND

Previous studies indicated that two-dimensional-susceptibility weighted imaging (2D-SWI) could serve as a useful biomarker for differentiating the grade of liver fibrosis.

PURPOSE

To evaluate the feasibility of 2D-SWI in the dynamic quantification of renal fibrosis in a rabbit model.

STUDY TYPE: Longitudinal study.

ANIMAL MODEL

Twenty-Four New Zealand White Rabbits including control group (n = 4); and renal fibrosis group (n = 20), by means of a unilateral ureteral obstruction (UUO) model.

FIELD STRENGTH/SEQUENCE

The 3.0 T SWI using a 2D gradient-echo sequence.

ASSESSMENT

The relative SWI signal ratio(r) of cortical and medulla (r = SI_renal/SI_muscle) was longitudinally assessed before ligation and on weeks 2, 4, 6, and 8 following ligation. Sirius Red staining was used to assess the degree of fibrosis in five high-power fields.

STATISTICAL TESTS

The repeated measures of analysis of variance and linear regression analysis.

RESULTS

Both the cortical and medullary r values were significantly higher in the UUO kidneys at week 2 compared with the kidneys before ligation. Over the course of UUO progression, significant changes occurred in the cortical and medullary r values in vivo and fibrosis scores in vitro (all P values < 0.05). The r values gradually decreased, while the fibrosis scores gradually increased over 8 weeks following ligation. The linear regression analysis showed a strong and significant correlation between cortical and medullary r values and the pathologic fibrosis scores (R² = 0.91, 0.81, respectively).

DATA CONCLUSION

The SWI sequence could provide a quantitative evaluation of renal fibrosis during UUO progression.

Level of Evidence: 2

Technical Efficacy Stage 1

J. Magn. Reson. Imaging 2017.

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Effects of government regulations on Manufacturer’s behaviors under carbon emission reduction

Abstract

This paper shifts the discussion of low-carbon technology from science to the economy, especially the reactions of a manufacturer to government regulations. One major concern in this paper is uncertainty about the effects of government regulation on the manufacturing industry. On the trust side, will manufacturers trust the government's commitment to strictly supervise carbon emission reduction? Will a manufacturer that is involved in traditional industry consciously follow a low-carbon policy? On the profit side, does equilibrium between a manufacturer and a government exist on deciding which strategy to undertake to meet a profit maximization objective under carbon emission reduction? To identify the best solutions to these problems, this paper estimates the economic benefits of manufacturers associated with policy regulations in a low-carbon technology market. The problem of an interest conflict between the government and the manufacturer is formalized as a game theoretic model, and a mixed strategy Nash equilibrium is derived and analyzed. The experiment results indicate that when the punishment levied on the manufacturer or the loss to the government is sizable, the manufacturer will be prone to developing innovative technology and the government will be unlikely to supervise the manufacturer.

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IJMS, Vol. 18, Pages 2703: Phylodynamic and Genetic Diversity of Canine Parvovirus Type 2c in Taiwan

IJMS, Vol. 18, Pages 2703: Phylodynamic and Genetic Diversity of Canine Parvovirus Type 2c in Taiwan

International Journal of Molecular Sciences doi: 10.3390/ijms18122703

Authors: Yung-Cheng Lin Shu-Yun Chiang Hung-Yi Wu Jih-Hui Lin Ming-Tang Chiou Hsin-Fu Liu Chao-Nan Lin

Canine parvovirus type 2c (CPV-2c) emerged in 2000 and is known for causing a more severe disease than other CPV-2 variants in puppies. In 2015, the emerging CPV-2c variant was isolated in Taiwan and it subsequently became the predominant variant. To trace the evolution of Taiwanese CPV-2c, we compared complete VP2 genes of CPV-2c from Taiwan and sequences obtained from GenBank. The evolutionary rate of CPV-2c was estimated to be 4.586 × 10−4 substitutions per site per year (95% highest posterior density (HPD) was 3.284–6.076 × 10−4). The time to the most recent common ancestor (TMRCA) dated to 1990 (95% HPD: 1984–1996) and 2011 (95% HPD: 2010–2013) for the CPV-2c variant and Taiwanese isolates, respectively. The CPV-2c variant isolated from Taiwan was clustered with CPV-2c from China. This phylogenetic clade began to branch off in approximately 2010 (95% HPD was 3.823–6.497). Notably, two unique mutations of Taiwanese CPV-2c were found, Q383R and P410L. In summary, this is the first report on the genome evolution of CPV-2c in Taiwan, revealing that this CPV-2c variant shares a common evolutionary origin with strains from China. The demographic history inferred by the Bayesian skyline plot showed that the effective population of CPV-2c increased until 2006 and then slowly declined until 2011.

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Role of Pharyngeal High Resolution Manometry and Impedance in Swallow Function of Head and Neck Cancer Patients

Conditions: Head and Neck Cancer; Dysphagia
Intervention: Diagnostic Test: pHRMi
Sponsor: Sidney Kimmel Comprehensive Cancer Center
Not yet recruiting

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Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update

Abstract

Purpose

To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma.

Methods

An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma.

Results

Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included.

Recommendations

Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or <0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of >1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

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Vaccines, Vol. 5, Pages 51: A Portrait of the Sialyl Glycan Receptor Specificity of the H10 Influenza Virus Hemagglutinin—A Picture of an Avian Virus on the Verge of Becoming a Pandemic?

Vaccines, Vol. 5, Pages 51: A Portrait of the Sialyl Glycan Receptor Specificity of the H10 Influenza Virus Hemagglutinin—A Picture of an Avian Virus on the Verge of Becoming a Pandemic?

Vaccines doi: 10.3390/vaccines5040051

Authors: Elena Schneider Jian Li Tony Velkov

Pandemic influenza is a constant global threat to human health. In particular, the pandemic potential of novel avian influenza viruses such as the H10N7 and H10N8 avian strains, which recently managed to cross the species barrier from birds to humans, are always of great concern as we are unlikely to have any prior immunity. Human and avian isolates of H10 influenza display the ability to rapidly adapt to replication in mammalian hosts. Fortunately, so far there is no evidence of efficient human-to-human transmission of any avian influenza virus. This review examines all of the available clinical and biological data for H10 influenza viruses with an emphasis on hemagglutinin as it is a major viral antigen that determines host range and immunity. The available glycan binding data on the influenza H10 hemagglutinin are discussed in a structure-recognition perspective. Importantly, this review raises the question of whether the emerging novel avian H10 influenza viruses truly represents a threat to global health that warrants close monitoring.

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Contents Vol. 94, 2017

Respiration 2017;94:I-VI

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Acknowledgement to the Reviewers

Respiration 2017;94:522-524

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Clinical applications and effectiveness of guided implant surgery: a critical review based on randomized controlled trials

Abstract

Background

Nowadays implant placement protocols are widespread among clinicians all over the world. However, available literature, only partially analyses what can be potential benefits for the clinicians and patients, often focusing just on specific aspects, such as accuracy. The purpose of this review is to compare computer guided implant placement with conventional treatment protocols.

Methods

A search strategy according to the P-I-C-O format was developed and executed using an electronic MEDLINE plus manual search from 2000 up to December 2016. This review included only randomized controlled trials (RCTs) focusing on subjects treated with digital workflow for oral implant placement compared to conventional procedures. Data were extracted from eligible papers and analysed. All kinds of outcomes were considered, even patient-related and economical outcomes.

Results

The search strategy revealed 16 articles; additional manual searches selected further 21 publications. Afterwards the evaluation of articles, only two studies could be selected for subsequent data extraction. The two identified RCTs analysed primary outcomes as prosthesis failure, implant failure, biological or prosthetic complications, and secondary outcomes as periimplant marginal bone loss. One RCT evaluated also the duration of treatment, post-surgical progress, additional treatment costs and patient satisfaction. The other RCT focused instead on evaluating eventual improvement of patient's quality of life. In both selected studies, were not observed by the authors statistically significant differences between clinical cases treated with digital protocols and those treated with conventional ones. In one RCT, however post-surgical progress evaluation showed more patients' self-reported pain and swelling in conventional group.

Conclusions

Within the limitation of this review, based on only two RCTs, the only evidence was that implant survival rate and effectiveness are similar for conventional and digital implant placement procedures. This is also confirmed by many other studies with however minor scientific evidence levels. Reduction of post-operative pain, surgical time and overall costs are discussed. Authors believe that scientific research should focus more in identifying which clinical situations can get greatest benefits from implant guided surgery. This should be done with research protocols such as RCT that assess comprehensively the advantages and disadvantages of fully digital surgical protocols.

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EMS Artwork: Treating an inmate in cardiac arrest

Artist's image shows a correctional facility's emergency response team aiding an inmate

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Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update

Abstract

Purpose

To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma.

Methods

Results

Recommendations

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Cardiomyokines from the heart

Abstract

The heart is regarded as an endocrine organ as well as a pump for circulation, since atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were discovered in cardiomyocytes to be secreted as hormones. Both ANP and BNP bind to their receptors expressed on remote organs, such as kidneys and blood vessels; therefore, the heart controls the circulation by pumping blood and by secreting endocrine peptides. Cardiomyocytes secrete other peptides besides natriuretic peptides. Although most of such cardiomyocyte-derived peptides act on the heart in autocrine/paracrine fashions, several peptides target remote organs. In this review, to overview current knowledge of endocrine properties of the heart, we focus on cardiomyocyte-derived peptides (cardiomyokines) that act on the remote organs as well as the heart. Cardiomyokines act on remote organs to regulate cardiovascular homeostasis, systemic metabolism, and inflammation. Therefore, through its endocrine function, the heart can maintain physiological conditions and prevent organ damage under pathological conditions.

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TP73 DNA methylation and upregulation of {Delta}Np73 are associated with an adverse prognosis in breast cancer

Aim

Accumulated evidence suggests that aberrant methylation of the TP73 gene and increased levels of Np73 in primary tumours correlate with poor prognosis. However, little is known regarding the transcriptional and functional regulation of the TP73 gene in breast cancer. The aim of the present study was to determine the expression of the Np73 isoform, its relationship with DNA methylation of TP73 and their clinical prognostic significance in breast cancer patients.

Methods

TP73 gene methylation was studied in TCGA datasets and in 70 invasive ductal breast carcinomas (IDCs). The expression of p73 isoforms was evaluated by immunohistochemistry (IHC) and Western blot and correlated with clinicopathological variables and clinical outcome.

Results

We observed that the methylation of diverse CpG islands of TP73 differed significantly between molecular subtypes. An inverse correlation was found between p73 protein expression and the methylation status of the TP73 gene. The expression of exon 3' of p73 (only expressed in Np73) was significantly higher in patients with wild-type p53. Immunohistochemical analysis revealed that all p73 isoforms were localised in both the nuclear and cytoplasmic compartments. We confirmed a positive association between the expression of Np73 and high histological grade.

Conclusions

Our findings suggest that high expression of Np73 could be used to determine the aggressiveness of IDCs and could be incorporated in the pathologist's report.

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Hb Baden: a rare high affinity haemoglobin variant and its management

Haemoglobin Baden is a rare variant haemoglobin which has only recently been clinically and functionally characterised. We present the case of a young adult male patient who presented with an erythrocytosis but was clinically asymptomatic. His mother was also diagnosed retrospectively having presented with erythrocytosis being treated with regular venesections. We discuss the management plan and potential significance of being a carrier of this rare haemoglobin variant.

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Prognostic value of vitamin D receptor and insulin-like growth factor receptor 1 expression in triple-negative breast cancer

Aim

Triple-negative breast cancer (TNBC) is characterised by shorter overall survival and an early peak of distant recurrences with still no specific targeted treatment available. Vitamin D receptor (VDR) and insulin-like growth factor receptor 1 (IGFR) have recently been described as potential new targets for anticancer therapy, yet their roles in TNBCs are still to be explored. In this study we investigated VDR and IGFR expression in patients with TNBC and compared them with clinical and pathological parameters and survival to possibly demonstrate their prognostic and therapeutic relevance.

Methods

The study included 96 patients with TNBC. Clinical and pathological parameters were compared with the immunohistochemical expression of VDR and IGFR.

Results

Positive VDR immunostaining was present in 27% of tumours and inversely correlated with higher mitotic score, histological grade and higher proliferation index measured by Ki-67 and related to the increased overall survival (OS). Out of 96 patients with TNBC, 35.5% of tumours were IGFR positive and correlated with higher mitotic score and Ki-67, and strongly correlated with shorter disease-free survival (DFS). Patients with VDR-negative and IGF-positive tumours had significantly lower DFS and OS.

Conclusion

Approximately one third of TNBCs express VDR and/or IGFR. Their expression is linked with the recurrence of the disease and survival, which make them possible targets for treatment and a prognostic tool for dividing TNBCs into more homogeneous subgroups.

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Clinical associations of the positive anti Ro52 without Ro60 autoantibodies: undifferentiated connective tissue diseases

Aims

Autoantibodies targeting Ro52 and Ro60 antigens are historically reported as anti SSA/Ro. In general anti SSA/Ro results are either anti Ro52+Ro60+ or anti Ro52–Ro60+ antibodies. Anti Ro52 without anti Ro60 (Ro52+ Ro60–) antibodies are often not reported routinely. This study intends to review the potential significance of these autoantibodies in the management of connective tissue diseases.

Method

A retrospective survey of Ro52+Ro60– was carried out as part of the service evaluation of extractable nuclear antigen antibodies (ENA) reporting from the immunology laboratory, the NHS Greater Glasgow and Clyde (GGC), UK. The clinical documents and laboratory results of 97 patients with Ro52+Ro60– and 100 patients with Ro52+Ro60+ were reviewed.

Results

Seventy-one patients (73%) with anti Ro52+Ro60– antibodies have been diagnosed with autoimmune conditions including undifferentiated connective tissue diseases (n=14, 14%), systemic lupus erythematosus (n=10, 10%), Sjögren's syndrome (n=10, 10%) and rheumatoid arthritis (n=13, 13%). Twenty-three patients (24%) with anti Ro52+Ro60– antibodies have no autoimmune features but were found to have significant clinical conditions including malignancies. In contrast, 87 patients (87%) with anti Ro52+Ro60+ antibodies have autoimmune conditions including Sjögren's syndrome (n=34, 34%), systemic lupus erythematosus (SLE; n=23, 23%), undifferentiated connective tissue diseases (n=12, 12%) and rheumatoid arthritis (n=6, 6%).

Conclusion

Anti Ro52 without anti Ro60 (Ro52+Ro60–) antibodies should be reported. In the majority of patients these autoantibodies were associated with various autoimmune diseases. Anti Ro52+Ro60– antibodies were also found in patients with significant clinical conditions including malignancies even though there was no suggestion of autoimmunity at the time of testing.

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How can we ensure that the coroners autopsy is not an invasion of human rights?

Background

Despite public inquiries, and some changes to legislation following high-profile multiple homicides that were not detected by autopsy, coroners continue to rely largely on the autopsy. Regardless of the extent of quality failings and excess deaths at some hospitals, not detected through the coroner system, the autopsy is scarcely used by hospitals to monitor standards and educate.

Objective

To explore when a compulsory medicolegal autopsy should, and should not, be used.

Method

Two hundred and thirty-six cases referred to a senior coroner were evaluated by pathologists with long experience of forensic, coronial and hospital autopsies, using detailed antecedent medical and circumstantial information: after their advice, the senior coroner decided what kind of autopsy provided sufficient information for his purposes.

Results

In nearly 40% (n=88) of deaths where the senior coroner accepted jurisdiction, issues raised could be resolved through analysis of medical records and antecedent information, supplemented only by detailed external examination of the body.

Conclusions

Timely provision of sufficient information allows informed decisions about the requirement for, and nature and extent of, medical investigations into a death: unnecessary post mortem dissection is avoided, protecting the rights, under Articles 8 and 9 of the Human Rights Act 1998, of the bereaved to privacy, family life and religious practice. Although improvements in healthcare can undoubtedly result from detailed coroners' inquiries, those deaths where the matters investigated relate only to the accuracy of a natural cause of death or sit with a healthcare provider's internal quality assurance, should be investigated by the healthcare system in collaboration with the bereaved.

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An evaluation of a coagulation system (Xprecia Stride) for utilisation in anticoagulation management

Aim

To evaluate the reliability and performance of the Xprecia Stride coagulometer under the conditions in which it is most likely to be used.

Methods

The performance of the Xprecia Stride coagulometer was compared with a local laboratory and the CoaguChek systems routinely used for international normalised ratio (INR) estimation within one primary and one secondary care based anticoagulation clinic in Birmingham. Anticoagulation clinic personnel were trained to use the Xprecia Stride. Patients attending the clinics were eligible if aged ≥18 years and had received warfarin for at least 3 months. Consenting participants provided capillary blood samples for parallel testing on the Xprecia Stride and CoaguChek systems. At the secondary care clinic, a venous blood sample was also collected for laboratory INR estimation. INR results were compared using linear regression analysis and Bland–Altman plots.

Results

A total of 102 laboratory and 205 parallel coagulometer INR tests were performed. Linear regression revealed strong correlation between the Xprecia Stride and the laboratory (r=0.83) and between the Xprecia Stride and CoaguChek systems (r=0.92). Within the therapeutic range, agreement between the systems was very good with 87% of the Xprecia Stride and laboratory INR results and 93% of the Xprecia Stride and CoaguChek INR results being within 0.5 INR units of each other.

Conclusion

INRs tested using the Xprecia Stride system showed good agreement with the laboratory and CoaguChek systems. Findings indicate that in the hands of the intended users the Xprecia Stride is accurate, reliable and acceptable for use in a routine clinical setting.

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Seasonality in airborne bacterial, fungal, and (1->3)-{beta}-D-glucan concentrations in two indoor laboratory animal rooms

Aims

The purpose of this study was to assess the temporal changes in the concentrations of bioaerosols in a laboratory mouse room (LMR) and laboratory rabbit room (LRR), and to determine environmental factors associated with the culturable bacteria, fungi and (1->3)-β-D-glucan concentrations.

Method

The concentrations of culturable airborne bacteria, fungi and (1->3)-β-D-glucan in the LMR and LRR were sampled once a month from March 2011 to February 2012. A single-stage viable cascade impactor was used to sample bacteria and fungi, while a two-stage cyclone bioaerosol sampler was used to collect airborne (1->3)-β-D-glucan.

Results

The culturable bacterial concentrations in the LMR showed a gradual increase during the summer. The culturable fungal concentrations showed similar seasonal patterns of change in the LMR and LRR with a noticeable increase during the summer. The (1->3)-β-D-glucan concentrations were highest during the warmer spring and summer months. Relative humidity (RH) was the environmental factor most associated with the concentrations of culturable bacteria and fungi. The overall airborne microbe concentrations were significantly higher in the LRR than in the LMR.

Conclusions

Airborne microbe concentrations in the LMR and LRR varied greatly depending on season, and these changes were affected by environmental factors.

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Liver allograft biopsies with histological cholestasis: a clinicopathological study of 254 cases from a single centre

Aims

Liver allograft biopsy is important in the management of liver transplant (LT) recipients. Cholestasis is an indicator of liver dysfunction, and histological evidence of cholestasis can be observed in a wide range of pathological entities in the post-LT setting. In this study, we describe the clinicopathological features and significance of liver allograft biopsies with histological cholestasis over 11 years in our centre.

Methods

Liver allograft biopsies performed in Queen Mary Hospital, Hong Kong from 2004 to 2014 showing histological cholestasis were retrieved from the pathology archive. Clinical and pathological data were retrospectively reviewed and analyzed.

Results

Among the 254 biopsies from 167 patients, large duct obstruction (LDO) and acute cellular rejection (ACR) were the two main aetiologies associated with cholestasis. There was a decrease in sepsis as a cause over the study duration. In cases showing cholestasis at 6 months or more after LT, LDO was more common than ACR. Over half (61%) of the 254 biopsies showed mild cholestasis. Severe panacinar cholestasis was more often observed in LDO. Mild cholestasis was most commonly observed regardless of the severity of ACR. Severe cholestasis was associated with poorer 1-year and 3-year graft survival and patient survival, as well as higher 3-month and 6-month post-biopsy mortality.

Conclusion

Histological cholestasis and its severity in liver allograft biopsies has clinical and prognostic significance. Our study summarizes our previous experience and provides further insights into the management of post-LT patients.

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Autopsy interrogation of emergency medicine dispute cases: how often are clinical diagnoses incorrect?

Aims

Emergency medicine is a 'high risk' specialty. Some diseases develop suddenly and progress rapidly, and sudden unexpected deaths in the emergency department (ED) may cause medical disputes. We aimed to assess discrepancies between antemortem clinical diagnoses and postmortem autopsy findings concerning emergency medicine dispute cases and to figure out the most common major missed diagnoses.

Methods

Clinical files and autopsy reports were retrospectively analysed and interpreted. Discrepancies between clinical diagnoses and autopsy diagnoses were evaluated using modified Goldman classification as major and minor discrepancy. The difference between diagnosis groups was compared with Pearson ² test.

Results

Of the 117 cases included in this study, 71 of cases (58 class I and 13 class II diagnostic errors) were revealed as major discrepancies (60.7%). The most common major diagnoses were cardiovascular diseases (54 cases), followed by pulmonary diseases, infectious diseases and so on. The difference of major discrepancy between the diagnoses groups was significant (p<0.001). Aortic dissection and myocardial infarction were the most common cause of death (15 cases for each disease) and the most common missed class I diagnoses (80% and 66.7% for each), higher than the average 49.6% of all class I errors of the study patients.

Conclusions

High major disparities between clinical diagnoses and postmortem examinations exist in emergency medical disputes cases; acute aortic dissection and myocardial infarction are the most frequently major missed diagnoses that ED clinicians should pay special attention to in practice. This study reaffirmed the necessity and usefulness of autopsy in auditing death in EDs.

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Vorwort zu Simon Runkel, Klangräume der Erlebnisgesellschaft. Eine phänomenologische Untersuchung

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Integrative Exekutivpolitik und Nachhaltigkeit - Herausforderungen für die Schweiz

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GSE104387 Purification of replicating pancreatic β-cells for gene expression studies

Contributors : Reyes Carballar ; Maria d Canyelles ; Claudia Fernández ; Yasmina Martí ; Sarah Bonnin ; Esther Castaño ; Eduard Montanya ; Noèlia Téllez
Series Type : Expression profiling by array
Organism : Rattus norvegicus

β-cell proliferation is a rare event in adult pancreatic islets. To study the replication-related β-cell biology we designed a replicating β-cells sorting system based on EdU incorporation for gene expression experiments.
The global transcriptome of replicating and quiescent pancreatic β-cells was analysed using gene expression arrays.

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Computed tomography scan based prediction of the vulnerable carotid plaque

Abstract

Background

Primary to validate a commercial semi-automated computed tomography angiography (CTA) –software for vulnerable plaque detection compared to histology of carotid endarterectomy (CEA) specimens and secondary validating calcifications scores by in vivo CTA with ex vivo non-contrast enhanced computed tomography (NCCT).

Methods

From January 2014 to October 2016 53 patients were included retrospectively, using a cross-sectional design. All patients underwent both CTA and CEA. Sixteen patients had their CEA specimen NCCT scanned. The semi-automated CTA software analyzed carotid stenosis using different HU values defining plaque components. The predictive values of CTA based detection of vulnerable plaques were calculated. Quantification of calcifications on CTA using region of interest (ROI)-function and mathematical equations was done manually, and validated by NCCT of the CEA specimen.

Results

The semi-automated CTA software had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 89.1% (95% CI, 73.6% - 96.4%), 31.3% (95% CI, 12.1% - 58.5%), 75% (95% CI, 59.3% - 86.2%) and 55.6% (95% CI, 22.6% - 84.6%). Strong correlation between in vivo CTA and ex vivo NCCT in quantification of calcification was observed, but CTA systematically underestimated calcificationsscore (CALS) with increasing calcification.

Conclusion

The CTA-software cannot be used in risk assessment of patients, due to poor specificity and NPV. The correlation between in vivo CTA and ex vivo NCCT was strong, proposing it to be used in both scientifically and clinical settings, but studies with larger sample sizes are needed.

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Synergistic effect of Carnosine on Browning of Adipose Tissue in Exercised Obese Rats ; A Focus on Circulating Irisin Levels

Abstract

Background: The recent appreciation of the energy burning capacity of brown adipose tissue turns it to an attractive target as anti-obesity therapy.

Objective: to evaluate the effect of L-carnosine on browning of white adipose tissue in exercised obese rats.

Methods: Sixty adult male Wistar albino rats between 7–8 weeks-old weighing 130–150 g were allocated into six groups;(i) normal control rats fed normal diet; (ii) high fat diet (HFD)-induced obese rats, (iii) normal control rats fed normal diet and injected with L-carnosine (250mg/kg), (iv) HFD-rats injected with L-carnosine (250mg/kg),(v): HFD-rats subjected to exercise training; (vi): HFD- rats subjected to exercise training and L-carnosine together. At the end of the experiment, the body weights and the serum levels of lipid profile, oxidative stress and inflammatory markers as well as circulating myokines are investigated. Gastrocnemius muscles and abdominal adipose tissues were excised for the measurement of gene expression of muscle irisin, adipose tissue uncoupling protein1 (UCP1), p38MAPK and CD137. In addition, histopathological examination for the studied groups was performed.

Results: Both exercise training and carnosine treatment significantly decreased body weight gain, ameliorated the induced dyslipidemia, reduced the thiobarbituric acid reactive species (TBARS) and TNF-?, while increased total antioxidant capacity and IL-10. Furthermore, serum irisin levels and relative. expression of adipose uncoupling protein-1 (UCP-1), adipose CD137 and fibronectin type III domain-containing protein 5(FNDC5), the precursor of irisin gene expression, were associated with the former improvements. The highest improvement was evident in the combined exercise and carnosine group.

Conclusion: These findings suggest that L-carnosine may induce browning of adipose tissue through irisin stimulation, a phenomenon that could be related to its antioxidant, anti-inflammatory and anti-obesity effect. This article is protected by copyright. All rights reserved

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GSE104387 Purification of replicating pancreatic β-cells for gene expression studies

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Vaccine and Therapeutic Options To Control Chikungunya Virus [Reviews]

SUMMARY

Beginning in 2004, chikungunya virus (CHIKV) went from an endemic pathogen limited to Africa and Asia that caused periodic outbreaks to a global pathogen. Given that outbreaks caused by CHIKV have continued and expanded, serious consideration must be given to identifying potential options for vaccines and therapeutics. Currently, there are no licensed products in this realm, and control relies completely on the use of personal protective measures and integrated vector control, which are only minimally effective. Therefore, it is prudent to urgently examine further possibilities for control. Vaccines have been shown to be highly effective against vector-borne diseases. However, as CHIKV is known to rapidly spread and generate high attack rates, therapeutics would also be highly valuable. Several candidates are currently being developed; this review describes the multiple options under consideration for future development and assesses their relative advantages and disadvantages.

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Buruli Ulcer, a Prototype for Ecosystem-Related Infection, Caused by Mycobacterium ulcerans [Reviews]

SUMMARY

Buruli ulcer is a noncontagious disabling cutaneous and subcutaneous mycobacteriosis reported by 33 countries in Africa, Asia, Oceania, and South America. The causative agent, Mycobacterium ulcerans, derives from Mycobacterium marinum by genomic reduction and acquisition of a plasmid-borne, nonribosomal cytotoxin mycolactone, the major virulence factor. M. ulcerans-specific sequences have been readily detected in aquatic environments in food chains involving small mammals. Skin contamination combined with any type of puncture, including insect bites, is the most plausible route of transmission, and skin temperature of <30°C significantly correlates with the topography of lesions. After 30 years of emergence and increasing prevalence between 1970 and 2010, mainly in Africa, factors related to ongoing decreasing prevalence in the same countries remain unexplained. Rapid diagnosis, including laboratory confirmation at the point of care, is mandatory in order to reduce delays in effective treatment. Parenteral and potentially toxic streptomycin-rifampin is to be replaced by oral clarithromycin or fluoroquinolone combined with rifampin. In the absence of proven effective primary prevention, avoiding skin contamination by means of clothing can be implemented in areas of endemicity. Buruli ulcer is a prototype of ecosystem pathology, illustrating the impact of human activities on the environment as a source for emerging tropical infectious diseases.

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2017 delivered humility, and proved our potential

Acting Editor in Chief Elizabeth Quill reflects on some of the top scientific stories of 2017.

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Enterovirus detection in patients with acute gastroenteritis in Switzerland

Abstract

Acute gastroenteritis (GE) has a major impact on morbidity and mortality worldwide, yet comprehensive data regarding infectious agents including enteroviruses are scarce. We hypothesized that enteroviruses constitute a significant cause of acute GE. We analyzed 677 stool samples from 504 patients, which had been submitted for suspected infectious GE. 0.2 ml of stool suspension was extracted using the Abbott m2000 _sp robot and analysed by multiplex nucleic acid testing (NAT) using the Luminex xTAG gastrointestinal pathogen panel (GPP) as well as by specific NATs detecting enteroviruses and polioviruses. Median age of the patients was 6.6 years (IQR 1.1-50.6; pediatric <18 years). 292 of 677 (43%) samples were positive for at least one pathogen. Enterovirus was detected in 5.3% (36/677) as sole pathogen (67%), and more frequently in children (p = 0.0054). Only rotavirus (18.6%) and norovirus (12.1%) were more frequent. Clostridium difficile and Campylobacter jejuni were detected in 5.5% and 2.2% of stools, respectively. Adenovirus, E. coli O157, Salmonella, Shiga toxin-producing E. coli (STEC), Shigella, Giardia lamblia, Cryptosporidium, and Entamoeba histolytica were rare (<1% of samples). Vibrio cholerae, Yersinia enterocolitica, enterotoxigenic E. coli (ETEC) and poliovirus were not detected. Thus, non-polio enteroviruses are the third most frequent pathogen in acute GE suggesting that enteroviruses may play an important role in GE even in developed, industrial health care settings. This article is protected by copyright. All rights reserved

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Lithium in Water Associated with Slower Rate of Alzheimer’s Disease Deaths

Rates of diabetes and obesity, which are important risk factors for Alzheimer's disease, also decrease if there is a particular amount of lithium in the water, says the study, published recently in the Journal of Alzheimer's Disease.

Postdoctoral fellow Val Fajardo and Rebecca MacPherson, Assistant Professor in the Department of Health Sciences, collected statistics on various lithium levels in drinking water in 234 counties across Texas. Lithium is a water-soluble alkali metal found in igneous rocks and mineral springs. It is commonly used to treat bipolar and other mood disorders, but at much higher doses than what occurs naturally in drinking water.

The research team, which included Associate Professor of Health Sciences Paul LeBlanc, compared lithium levels naturally found in tap water with Alzheimer's disease mortality rates, along with the incidence of obesity and diabetes, in the Texas counties. "We found counties that had above the median level of lithium in tap water (40 micrograms per litre) experienced less increases in Alzheimer's disease mortality over time, whereas counties below that median level had even higher increases in Alzheimer's deaths over time," says Fajardo.

The frequency of obesity and Type 2 diabetes also went down when the drinking water contained similar lithium levels, the researchers found. Fajardo says he and his team focused on Texas because data on lithium levels were "freely available."

Previous studies have demonstrated lithium's ability to protect against Alzheimer's disease, obesity and diabetes. "However, we are one of the first groups to show that lithium's potential protective effect against Alzheimer's disease, obesity and diabetes may translate to the population setting through very low levels of lithium in tap water," says Fajardo.

The Brock research comes on the heels of a study from the University of Copenhagen in August 2017 (see here) linking high lithium levels in drinking water to decreases in dementia rates. But Fajardo warns it's too early to start advising authorities to add lithium to drinking water. "There's so much more research we have to do before policy-makers look at the evidence and say, OK, let's start supplementing tap water with lithium just like we do in some municipalities with fluoride to prevent tooth decay," he says.

Postdoctoral fellow Val Fajardo, left, and Rebecca MacPherson, Assistant Professor in the Department of Health Sciences, are researching the impact of lithium in drinking water on Alzheimer's disease.

###

NOTES FOR EDITORS
Full study: Fajardo VA, Fajardo VA, LeBlanc PJ, MacPherson REK (2018) Examining the Relationship between Trace Lithium in Drinking Water and the Rising Rates of Age-Adjusted Alzheimer's Disease Mortality in Texas, J Alzheimers Dis 61 425–434 (doi: 10.3233/JAD-170744)

Contact
Name: Dan Dakin, Media Relations Officer, Brock University
Tel: +1 905 688 5550 ext.5353
Email: ddakin@brocku.ca

ABOUT THE JOURNAL OF ALZHEIMER'S DISEASE
The Journal of Alzheimer's Disease (j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 3.731 according to the 2016 Journal Citation Reports (Clarivate Analytics, 2017). The journal is published by IOS Press (iospress.com).

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Thauera sinica sp. nov., a phenol derivative-degrading bacterium isolated from activated sludge

Abstract

A bacterial strain, K11^T, capable of degrading phenol derivatives was isolated from activated sludge of a sewage treatment plant in China. This strain, which can degrade more than ten phenol derivatives, was identified as a Gram-stain negative, rod-shaped, asporogenous, facultative anaerobic bacterium with a polar flagellum. The strain was found to grow in tryptic soy broth in the presence of 0–2.5% (w/v) NaCl (optimum 0–1%), at 4–43 °C (optimum 30–35 °C) and pH 4.5–10.5 (optimum 7.5–8). Comparative analysis of nearly full-length 16S rRNA gene sequences showed that this strain belongs to the genus Thauera. The 16S rRNA gene sequence was found to show high similarity (97.5%) to that of Thauera chlorobenzoica 3CB-1^T, with lesser similarity to other recognised Thauera strains. The G+C content of the DNA of the strain was determined to be 67.8 mol%. The DNA–DNA hybridization value between K11^T and Thauera aromatica DSM6984^T was 10.4 ± 4.5%. The genomic OrthoANI values of K11^T with the other nine type strains of genus Thauera were less than 81.1%. Chemotaxonomic analysis of strain K11^T revealed that Q-8 is the predominant quinone; the polar lipids contain phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and five uncharacterised lipids; the major cellular fatty acid was identified as summed feature 3 (C_16:1ω7c and/or iso-C_15:0 2-OH; 45.9%), followed by C_16:0 (20.5%) and C_18:1ω7c (15.8%). Based on the phenotypic and phylogenetic evidence, DNA–DNA hybridisation, OrthoANI, chemotaxonomic analysis and results of the physiological and biochemical tests, a new species named Thauera sinica sp. nov. is proposed with strain K11^T (= CGMCC 1.15731^T = KACC 19216^T) designated as the type strain.

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IJMS, Vol. 18, Pages 2708: Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo

IJMS, Vol. 18, Pages 2708: Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo

International Journal of Molecular Sciences doi: 10.3390/ijms18122708

Authors: Teruhisa Takagishi Takafumi Hara Toshiyuki Fukada

Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular machineries and influences physiological events, such as systemic growth, bone homeostasis, skin formation, immune responses, endocrine function, and neuronal function. Zn transporters are thought to mainly contribute to Zn homeostasis within cells and in the whole body. Recent genetic, cellular, and molecular studies of Zn transporters highlight the dynamic role of Zn as a signaling mediator linking several cellular events and signaling pathways. Dysfunction in Zn transporters causes various diseases. This review aims to provide an update of Zn transporters and Zn signaling studies and discusses the remaining questions and future directions by focusing on recent progress in determining the roles of SLC39A/ZIP family members in vivo.

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IJMS, Vol. 18, Pages 2702: The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms

IJMS, Vol. 18, Pages 2702: The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms

International Journal of Molecular Sciences doi: 10.3390/ijms18122702

Authors: Yue-Wern Huang Melissa Cambre Han-Jung Lee

Nanotechnology is an emerging discipline that studies matters at the nanoscale level. Eventually, the goal is to manipulate matters at the atomic level to serve mankind. One growing area in nanotechnology is biomedical applications, which involve disease management and the discovery of basic biological principles. In this review, we discuss characteristics of nanomaterials, with an emphasis on transition metal oxide nanoparticles that influence cytotoxicity. Identification of those properties may lead to the design of more efficient and safer nanosized products for various industrial purposes and provide guidance for assessment of human and environmental health risk. We then investigate biochemical and molecular mechanisms of cytotoxicity that include oxidative stress-induced cellular events and alteration of the pathways pertaining to intracellular calcium homeostasis. All the stresses lead to cell injuries and death. Furthermore, as exposure to nanoparticles results in deregulation of the cell cycle (i.e., interfering with cell proliferation), the change in cell number is a function of cell killing and the suppression of cell proliferation. Collectively, the review article provides insights into the complexity of nanotoxicology.

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IJMS, Vol. 18, Pages 2704: In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

IJMS, Vol. 18, Pages 2704: In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

International Journal of Molecular Sciences doi: 10.3390/ijms18122704

Authors: Jae Park

p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39) and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39) and in silico scores (Avg. score; −27.5 to −29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3) were found to inhibit p38 MAPK by 27–31% (p < 0.05) better than those with less scores (ΔE < −27.0). Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2) inhibited p38 MAPK (IC50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; −29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05) in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may be a most potent p38 MAPK inhibitor among the tested compounds and the combining in silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules.

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Outcome of children and adolescents with central nervous system tumors in phase I trials

Abstract

Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0–17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90–100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.

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Modified Medical Research Council Dyspnea Scale in GOLD Classification Better Reflects Physical Activities of Daily Living

BACKGROUND:In multidimensional Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, the choice of the symptom assessment instrument (modified Medical Research Council dyspnea scale [mMRC] or COPD assessment test [CAT]) can lead to a different distribution of patients in each quadrant. Considering that physical activities of daily living (PADL) is an important functional outcome in COPD, the objective of this study was to determine which symptom assessment instrument is more strongly associated with and differentiates better the PADL of patients with COPD.METHODS:The study included 115 subjects with COPD (GOLD 2–4), who were submitted to spirometry, the mMRC, the CAT, and monitoring of PADL (triaxial accelerometer). Subjects were divided into 2 groups using the cutoffs proposed by the multidimensional GOLD classification: mMRC < 2 and ≥ 2 and CAT < 10 and ≥ 10.RESULTS:Both mMRC and CAT reflected the PADL of COPD subjects. Subjects with mMRC < 2 and CAT < 10 spent less time in physical activities < 1.5 metabolic equivalents of task (METs) (mean of the difference [95% CI] = −62.9 [−94.4 to −31.4], P < .001 vs −71.0 [−116 to −25.9], P = .002) and had a higher number of steps (3,076 [1,999–4,153], P < .001 vs 2,688 [1,042–4,333], P = .002) than subjects with mMRC > 2 and CAT > 10, respectively. Physical activities ≥ 3 METs differed only between mMRC < 2 and mMRC ≥ 2 (39.2 [18.8–59.6], P < .001). Furthermore, only the mMRC was able to predict the PADL alone (time active, r2 = 0.16; time sedentary, r2 = 0.12; time ≥ 3 METs, r2 = 0.12) and associated with lung function (number of steps, r2 = 0.35; walking time, r2 = 0.37; time < 1.5 METs, r2 = 0.25).CONCLUSIONS:The mMRC should be adopted as the classification criterion for symptom assessment in the GOLD ABCD system when focusing on PADL.

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Heart Rate Variability in Extremely Preterm Infants Receiving Nasal CPAP and Non-Synchronized Noninvasive Ventilation Immediately After Extubation

INTRODUCTION:There is a paucity of studies comparing the physiological effects of nasal CPAP or non-synchronized noninvasive ventilation (ns-NIV) during the postextubation phase in preterm infants. Heart rate variability (HRV) can identify system instability before clinical or laboratory signs of deterioration. Thus, we sought to investigate any differences in HRV between those modes.METHODS:15 preterm infants with birthweight ≤1,250 g and undergoing their first extubation attempt were studied immediately after disconnection from mechanical ventilation. Electrocardiogram (ECG) recordings were obtained while on nasal CPAP and ns-NIV in a random order (30–60 min on each). Time and frequency domain analyses were used to calculate HRV from 5-min segments of ECG.RESULTS:12 of 15 infants were analyzed (3 were excluded for low ECG quality): 7 successes and 5 failures. HRV parameters were higher during ns-NIV when compared to nasal CPAP, but differences were not statistically different. However, absolute and relative differences in HRV values (all time domain parameters) were significantly higher in infants who failed extubation during ns-NIV.CONCLUSIONS:Nasal CPAP or ns-NIV provided immediately postextubation did not affect HRV. Interestingly, in an exploratory analysis, changes in HRV did occur during ns-NIV in the subgroup of infants who failed extubation. Hence, changes in HRV as early as 2 h after extubation should be further explored in larger studies as a potential predictor of postextubation respiratory failure.

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Perceived Satisfaction With Long-Term Oxygen Delivery Devices Affects Perceived Mobility and Quality of Life of Oxygen-Dependent Individuals With COPD

BACKGROUND:Although routine physical activity for individuals with COPD is recommended, there are inherent limitations of available oxygen delivery devices that may result in hypoxemia during activity. Changes in Medicare laws have resulted in an increased use of oxygen cylinders and a reduction in the use of liquid oxygen devices. The aim of this survey was to assess the impact of perceived satisfaction with various oxygen delivery devices on perceived mobility and quality of life (QOL) of oxygen-dependent subjects with COPD.METHODS:A survey was developed to measure perceived satisfaction with current portable oxygen delivery devices, perceived mobility, and perceived QOL. The survey was deployed via a link posted on the COPD Foundation's COPD360SOCIAL social media site for 5 weeks, which resulted in the recruitment of 529 participants, of which 417 were included in the data analysis.RESULTS:Quantile regression analysis revealed that the median perceived device satisfaction score was significantly higher in the liquid oxygen device group (P < .001) compared with the portable oxygen cylinder and portable oxygen concentrator (POC) groups. The median perceived mobility score was significantly higher in the liquid oxygen device group (P < .001) compared with the portable oxygen cylinder group, but not the POC group. The median QOL score was significantly higher in the liquid oxygen device group (P < .001) compared with the POC and portable oxygen cylinder groups. Moreover, partial least-squares structural equation modeling regression analysis showed that perceived mobility is significantly affected by perceived satisfaction with the long-term oxygen therapy (LTOT) device (adjusted R2 = 0.15, P < .001), and perceived QOL is significantly affected by both perceived satisfaction with the LTOT device and perceived mobility (adjusted R2 = 0.45, P < .001).CONCLUSIONS:For individuals with COPD requiring LTOT, perceived satisfaction with a portable LTOT device significantly and positively affects perceived mobility and QOL.

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A Quality Improvement Project to Improve Evidence-Based Inhaled Nitric Oxide Use

BACKGROUND:Inhaled nitric oxide (INO) reduces extracorporeal membrane oxygenation (ECMO) use in term and near-term neonates with persistent pulmonary hypertension of the newborn; however, its overutilization is increasing. We hypothesized that implementing a shared baseline protocol would safely improve evidence-based INO use in a Level IV neonatal ICU.METHODS:Through several plan-do-study-act cycles, a shared baseline protocol for initiation and weaning of INO was developed and implemented starting in August 2014. Based on user feedback, the shared baseline protocol was amended and re-evaluated at regular intervals. Significant changes for process and outcome measures related to utilization of INO were detected using statistical process control, bivariate analyses using t test or nonparametric Wilcoxon rank-sum test as appropriate, and chi-square and Fisher exact testing as appropriate. Comparisons between the pre-plan-do-study-act group (January 2012 to July 2014) and post-plan-do-study-act group (August 2014 to October 2015) were made.RESULTS:One hundred sixteen INO courses in 95 subjects were administered during the pre-plan-do-study-act period, and 44 episodes were initiated in 39 subjects during the post-plan-do-study-act period. Process control charts demonstrate significant reductions in the percentage of INO doses > 20 ppm and the percentage of prolonged (>4-d) INO courses. Prolonged INO courses decreased from 67.9 to 40% (P = .032), whereas the median duration of INO per course decreased from 8 to 4 d (P < .001). The percentage of INO courses that exceeded the dose of 20 ppm decreased from 18.1 to 2.3% (P = .009). Very delayed INO weaning (weaning at FIO2 ≤ 0.40) decreased from 41.9 to 21.2% (P = .038). There were no differences in the percentage of INO courses administered to non-sedated subjects or the percentage of INO courses administered to preterm infants. There was no difference for death or ECMO between groups.CONCLUSIONS:Implementation of a shared baseline protocol to encourage appropriate INO initiation and weaning safely decreased INO exposures. Focused efforts on reducing unapproved INO use in preterm infants are warranted.

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COPD and Physical Activity: A Call to Action for Respiratory Therapists and Patients

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Editor's Commentary

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Emergency Department Blood Gas Utilization and Changes in Ventilator Settings

BACKGROUND:Mechanically ventilated patients increasingly spend hours in emergency department beds before ICU admission. This study evaluated the performance of blood gases in mechanically ventilated subjects in the emergency department and subsequent changes to mechanical ventilation settings.METHODS:This was a multi-center, prospective, observational study of subjects ventilated in the emergency department, conducted at 3 academic emergency departments from July 2011 to March 2013. We measured the rate of arterial blood gas (ABG) and venous blood gas (VBG) analysis, and we assessed the associations between the conditions of hypoxemia, hyperoxia, hypercapnia, or acidemia and changes to mechanical ventilator settings.RESULTS:Of 292 ventilated subjects, 17.1% did not have a blood gas sent in the emergency department. Ventilator changes were made significantly more frequently for subjects who had an ABG as the initial blood gas sent in the emergency department (odds ratio 2.70, 95% CI 1.46–4.99, P = .002). However, findings of hypoxemia, hyperoxia, hypercapnia, or acidemia were not correlated with ventilator adjustments.CONCLUSIONS:In this prospective observational study of subjects mechanically ventilated in the emergency department, the majority had a blood gas checked while in the emergency department. While ABGs were associated with having changes made to ventilator settings in the emergency department, clinical findings of hypoxemia, hyperoxia, hypercapnia, and acidemia were not. Inattention to blood gas results may lead to missed opportunities in guiding ventilator changes in the emergency department.

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Utilizing Respiratory Therapists to Reduce Costs of Care

INTRODUCTION:Changes to the reimbursement of respiratory care services over the past 26 years make it imperative that respiratory therapists (RTs) demonstrate cost savings to establish their value. Therefore, this systematic review evaluated the cost-related impacts from utilizing RTs to deliver care when compared to other care providers.METHODS:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to guide the search process. The study addressed articles across all age groups and care settings that compared the cost of care provided by RTs to a comparison group. Studies were excluded if they were not written in English, described care provided outside of the United States, did not provide quantitative data, or lacked a comparison group.RESULTS:A total of 4,120 articles emerged from the search process, of which 60 qualified for a full text review. Cost savings were evaluated for the 28 articles included in this review, noting the study design, the specific respiratory care practice, use of protocols, clinical setting, and age group. The most frequently studied topic was mechanical ventilation, which along with disease management represented by the most randomized, controlled trials for the study design. The clinical practice area notably absent was home care.CONCLUSIONS:Although cost comparisons across studies could not be made due to the inconsistent manner in which data were reported, evidence demonstrated that care provided by RTs yielded both direct and indirect cost reductions, which were achieved through protocol utilization, specialized expertise, and autonomous decision making. The care provided was consistent with care provided by other disciplines. It is critical for the respiratory care profession to highlight key clinical practice areas for future research, to establish uniform reporting measures for outcomes, and to foster the development of future respiratory care researchers to affirm the value that respiratory therapists add to patient care.

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Economic Assessment of 4 Approaches to the Diagnosis and Initial Treatment of Sleep Apnea

BACKGROUND:A dilemma faced by health-care administrators is that need greatly outstrips capacity for diagnosing and treating sleep apnea, with such decisions carrying significant economic consequences. Our objective was to develop an economic model to estimate the relative costs of 4 approaches for diagnosis and initial treatment of sleep apnea.METHODS:The analysis consisted of developing a mathematical model depicting possible diagnostic and treatment approaches to the care of patients with sleep apnea; developing 4 clinical scenarios to describe distinct approaches to the management of sleep apnea patients (in-laboratory, unattended, direct-to-autotitrating PAP [auto-PAP], and mixed); and identifying costs associated with each scenario. We created a hypothetical cohort of 1,000 patients with 85% prevalence of sleep apnea to generate cost estimates.RESULTS:The driver of per-patient costs was the total number of sleep studies, which varied widely across scenarios: from 425 for the direct-to-auto-PAP approach to 1,441 in the unattended approach. The scenarios also differed in per-patient costs: Per-patient costs excluding facility startup costs were $456 for direct-to-auto-PAP, $913 for in-laboratory, $991 for mixed, and $1,090 for unattended.CONCLUSIONS:Approaches to diagnosing and treating sleep apnea that emphasized early application of auto-PAP had lower per-patient costs.

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Ecological Validity in the Critical Care Environment: Closing the Loop on Evidence Based Medicine

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Maternal Stress During Pregnancy and Allergic Diseases in Children During the First Year of Life

BACKGROUND:Many recent studies indicate that prenatal maternal distress increases the risk of allergic diseases in children. The mechanisms that favor it are still unclear. OBJECTIVES: We aimed to assess the association between exposure to different kinds of prenatal stress and the occurrence of atopic dermatitis, food allergy, wheezing, and recurrent respiratory tract infections in children.METHODS:The study population consisted of 370 mother–child pairs from a Polish Mother and Child Cohort (REPRO_PL). The analysis was restricted to the women who worked at least one month during the pregnancy period. Maternal psychological stress during pregnancy was assessed based on the Subjective Work Characteristics Questionnaire, the Perceived Stress Scale, and the Social Readjustment Rating Scale. The presence of atopic dermatitis, food allergy, wheezing, and recurrent respiratory tract infections in children was evaluated by doctors at 12 months of age.RESULTS:In a univariate model, we showed significant association between maternal life stress (according to the Perceived Stress Scale) and stressful life events (according to the Social Readjustment Rating Scale) and infant wheezing (at least 1 episode of wheezing during the first year of life). A multivariate model of logistic regression analysis revealed that maternal stress during pregnancy, described by the Social Readjustment Rating Scale, increased the risk of wheezing in children (OR 1.09, 95% CI 1.01–1.02) independently from other predictors of wheezing previously determined in this cohort, such as the number of infections and maternal smoking. We observed also significant positive association between maternal life stress during pregnancy measured by the Perceived Stress Scale and the risk of recurrent respiratory tract infections in the first year of life, however it was not significant after adjustment for confounding variables.CONCLUSIONS:Maternal stress during pregnancy increases the risk of childhood wheezing. The effects of stress during pregnancy on the onset of allergic diseases in children should be developed and translated into early prevention strategies.

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Airway Pressure Release Ventilation Letter—Reply

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Atmosphere, Vol. 8, Pages 251: An Evaluation of the CHIMERE Chemistry Transport Model to Simulate Dust Outbreaks across the Northern Hemisphere in March 2014

Atmosphere, Vol. 8, Pages 251: An Evaluation of the CHIMERE Chemistry Transport Model to Simulate Dust Outbreaks across the Northern Hemisphere in March 2014

Atmosphere doi: 10.3390/atmos8120251

Authors: Bertrand Bessagnet Laurent Menut Augustin Colette Florian Couvidat Mo Dan Sylvain Mailler Laurent Létinois Véronique Pont Laurence Rouïl

Mineral dust is one of the most important aerosols over the world, affecting health and climate. These mineral particles are mainly emitted over arid areas but may be long-range transported, impacting the local budget of air quality in urban areas. While models were extensively used to study a single specific event, or make a global analysis at coarse resolution, the goal of our study is to simultaneously focus on several affected areas—Europe, North America, Central Asia, east China and the Caribbean area—for a one-month period, March 2014, avoiding any parameter fitting to better simulate a single dust outbreak. The simulation is performed for the first time with the hemispheric version of the CHIMERE model, with a high horizontal resolution (about 10 km). In this study, an overview of several simultaneous dust outbreaks over the Northern Hemisphere is proposed to assess the capability of such modeling tools to predict dust pollution events. A quantitative and qualitative evaluation of the most striking episodes is presented with comparisons to satellite data, ground based particulate matter and calcium measurements. Despite some overestimation of dust concentrations far from emission source areas, the model can simulate the timing of the arrival of dust outbreaks on observational sites. For instance, several spectacular dust storms in the US and China are rather well captured by the models. The high resolution provides a better description and understanding of the orographic effects and the long-range transport of dust plumes.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2iWCPqe

A prospective, randomized, double-blinded control study on comparison of tramadol, clonidine and dexmedetomidine for post spinal anesthesia shivering

Publication date: January–February 2018
Source:Brazilian Journal of Anesthesiology (English Edition), Volume 68, Issue 1
Author(s): Rajagopalan Venkatraman, Krishnamoorthy Karthik, Anand Pushparani, Annadurai Mahalakshmi
IntroductionShivering, a common intraoperative problem under spinal anesthesia increases the oxygen consumption considerably and is uncomfortable and distressing to the patient, anesthesiologist as well as surgeon. The present study was designed to explore the effectiveness of tramadol, clonidine and dexmedetomidine in the treatment of post spinal anesthesia shivering and to look for their adverse effects.MethodsThis prospective, randomized, double blinded control study was done on 90 patients who developed shivering under spinal anesthesia. They were randomly allocated into three groups with Group T receiving tramadol 1mg.kg⁻¹, Group C getting clonidine 1mcg.kg⁻¹ and Group D patients receiving dexmedetomidine 0.5mcg.kg⁻¹. The time taken to control shivering, recurrence rate, hemodynamic variables, sedation score and adverse effects were observed.ResultsDexmedetomidine was faster in the control of shivering in 5.7±0.79minutes (min) whereas tramadol took 6.76±0.93min and clonidine was slower with 9.43±0.93min. The recurrence rate was much lower in the dexmedetomidine group with 3.3% than for clonidine (10%) and tramadol (23.3%) group. The sedation achieved with dexmedetomidine was better than clonidine and tramadol. The tramadol group had more cases of vomiting (four) and dexmedetomidine group had six cases of hypotension and two cases of bradycardia. Two of the clonidine patients encountered bradycardia and hypotension.ConclusionDexmedetomidine is better than tramadol and clonidine in the control of shivering because of its faster onset and less recurrence rate. Though complications are encountered in the dexmedetomidine group, they are treatable.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BjRKFS

Atelectasis in postoperative bariatric surgery: how many understand them?

Publication date: January–February 2018
Source:Brazilian Journal of Anesthesiology (English Edition), Volume 68, Issue 1
Author(s): Luiz Albert Forgiarini, Antonio M. Esquinas

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Erratum of “Optimizing post-operative pain management in Latin America”

Publication date: January–February 2018
Source:Brazilian Journal of Anesthesiology (English Edition), Volume 68, Issue 1
Author(s): João Batista Santos Garcia, Patricia Bonilla, Durval Campos Kraychete, Fernando Cantú Flores, Elizabeth Diaz Perez de Valtolina, Carlos Guerrero

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BjRAhK

Fatal cardiac tamponade that developed in the Post-Anesthesia Care Unit: a rare complication after lung lobectomy

Publication date: Available online 12 December 2017
Source:Brazilian Journal of Anesthesiology (English Edition)
Author(s): Hyung Mook Lee, Young Jae Jeon, Hye Won Chung, Hyo Min Yun, Mi Hyun Kim
Background and objectivesCardiac tamponade is potentially fatal medical condition, which rarely occurs as a complication of lung lobectomy. We present the first case of cardiac tamponade to develop in a Post-Anesthesia Care Unit following a lung lobectomy.Case reportA 54-year-old man with pulmonary squamous cell carcinoma underwent an apparently uncomplicated lung lobectomy. His hemodynamics was unremarkable throughout the surgery and initially in the Post-Anesthesia Care Unit. However, after 5min in the Post-Anesthesia Care Unit, he suddenly became hypotensive and dyspneic. He responded poorly to inotropics and fluid resuscitation. Transesophageal echocardiography conducted by an anesthesiologist who suspected a cardiac etiology revealed a pericardial effusion compressing the heart. After a failed attempt of pericardiocentesis, an emergency pericardial window operation was performed. The patient improved dramatically once the heart was decompressed.ConclusionSince cardiac tamponade is generally not suspected as a cause of hemodynamic instability after a lung lobectomy, as it was in this case, a misdiagnosis of the patient's condition may have led to improper management resulting in death. As anesthesiologists are often involved in the initial resuscitation of morbid patients in Post-Anesthesia Care Units, their acquaintance with various postoperative complications and competence in echocardiography for assessing cardiac problems may contribute to patient survival.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2j0lCMM

Study of different environmental matrices to access the extension of metal contamination along highways

Abstract

Metals are indicators of contamination by anthropic activities, such as road traffic. To assess the extent of the metal contamination, more comprehensive studies analyzing different environmental matrices, such as soils, dust, and plants, collected in different sites that are potential sources of these pollutants along the highways, must be prioritized. Samples of soils, dust, and plants were collected alongside the highways of Brazil at 20 sites selected in strategic locations of metal accumulation (Cr, Pb, Zn, As, and Sb) or different situations of the high ways during two rain conditions (wet and dry weeks of sampling): nearby gutters and water supplies, tolls, petrol stations, a federal road police station, and areas associated with agriculture (yearly culture planting upstream of the highway). The geoaccumulation index (metal concentration in the sample of interest/background) varied from 0 to 6, and the decreasing order of contamination by metals during the wet and dry periods were, respectively: Zn > As > Pb = Sb > Cr and Zn > As > Pb > Cr > Sb. In the soils near the highways, the highest concentrations of metals were as follows (mg kg⁻¹): As = 15.6, Cr = 81.9, Pb = 39.7, Sb = 5.0, and Zn = 379.3. The highest amounts of these elements in the most superficial layer in soils indicated their addition through atmospheric emissions. The most prominent metal was Sb, whose concentration was greater than the quality limits for soils. The concentration of Sb in soils was higher in the wet week than in the dry week. The emissions from road traffic promoted the increase in metals in the dust on the track, especially Zn and Pb. The highest metal concentrations in grasses (Brachiaria) were found in the roots, except for Sb and Zn, which suggests leaf absorption of atmospheric deposition. Metal contamination was widespread in all studied matrices along the highways.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ARLDpu

Evaluation of disinfection by-product formation during chlor(am)ination from algal organic matter after UV irradiation

Abstract

This study evaluated the effect of low-pressure ultraviolet (UV) irradiation on the formation of disinfection by-products (DBPs) from algal organic matter of Microcystis aeruginosa during subsequent chlorination and chloramination. The algal organic matter includes extracellular organic matter (EOM) and intracellular organic matter (IOM). The fluorescence excitation-emission matrix spectra indicated that the humic/fulvic acid-like organics of EOM and the protein-like organics of IOM may be preferentially degraded by UV treatment. UV irradiation with low specific UV absorbance values was effective in reducing the formation of trihalomethanes and dichloroacetic acid from EOM and IOM during the subsequent chlorination. During the UV-chloramine process, higher UV dose (1000 mJ/cm²) led to the decrease of the formation of dichloroacetic acid, trichloroacetic acid, and haloketones from IOM by an average of 24%. Furthermore, UV irradiation can slightly increase the bromine substitution factors (BSFs) of haloacetic acids from EOM during chlorination, including dihaloacetic acids and trihaloacetic acids in the presence of bromide (50 μg/L). However, UV irradiation did not shift the formation of DBPs from IOM to more brominated species, since the BSFs of trihalomethanes, dihaloacetic acids, trihaloacetic acids, and dihaloacetonitriles almost kept unchanged during UV-chlorine process. As for UV-chloramine process, UV irradiation decreased the BSFs of trihalomethanes, while increased the BSFs of dihaloacetic acid for both EOM and IOM. Overall, the UV pretreatment process is a potential technology in treating algae-rich water.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ASb2zq

Application potential of aerobic denitrifiers coupled with a biostimulant for nitrogen removal from urban river sediment

Abstract

Aerobic denitrifiers coupled with a denitrification agent were applied in the sediment of an urban river for the bioremediation of nitrogen pollution. The results revealed that 14.7% of the total nitrogen in the sediment was removed after 115 days of treatment and the nitrate nitrogen concentration removal rate was enhanced in the overlying water. Compared with the control, the total transferable nitrogen in the sediment increased from 0.097 to 0.166 mg/g, indicating that more nitrogen is likely to be involved in the biogeochemical cycling of nitrogen. Increased urease activity indicated the possible further potential of nitrogen biodegradation, while the decreased protease pointed to the low concentration of protein remaining in the sediment. Sequencing revealed that the bacterial community diversity in the sediment increased significantly after 43 days of treatment and that the effect persisted. Compared with other microcosms, the dominant phyla in the sediment after 43 days were Firmicutes, Elusimicrobia, Spirochaetae and Fibrobacteres; whereas, after 115 of treatment, the dominant bacteria were Nitrospirae, Deferribacteres and Chloroflexi. The dominant bacteria in the sediment are mainly associated with nitrogen cycling and thus contributed considerably to nitrogen removal in the sediment. Overall, the direction of species succession was similar to natural succession; namely, there were no undesirable ecological risks involved. This study highlights the possible benefits and feasibility of using bioaugmentation technology coupled with biostimulation to remediate nitrogen-polluted sediments.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2nTzcqm

Management of Slipped Gastric Bands via Creation of a De Novo Tunnel and Band Replacement: a Single-Centre Experience

Abstract

Background

A lack of clarity remains over the optimal strategy for the management of laparoscopic adjustable gastric band (LAGB) slippage, which, although rare (around 3% in our experience), can when acute result in obstruction, gastric erosion or ischaemia. Typically, slipped bands are removed acutely. The aim of this study was to explore outcomes following immediate or delayed resiting of slipped LAGBs in a single centre, comparing simple repositioning with retunnelling and replacement.

Methods

A retrospective analysis of computerised records, notes and prospectively maintained bariatric databases was undertaken to identify all patients with a slipped LAGB in a single centre.

Results

Thirty-two patients required operative intervention following a diagnosis of slipped LAGB (median time from initial LAGB insertion to slippage 2.9 years). Two (6%) patients underwent band removal and 30 (94%), band revision surgery (25 immediately and five at a planned but expedited procedure).Twenty-four (77%) patients underwent insertion of a new LAGB via a de novo retrogastric tunnel, five (21%) of which required further future operative intervention; whereas, six (23%) patients underwent repositioning of the existing LAGB within the same tunnel, five (83%) of which underwent further operative intervention (log-rank test p = 0.0001). Following LAGB revision, there was no significant further change in BMI (median + 1 kg/m²; range − 13 to + 10 kg/m²).

Conclusion

Resiting of slipped LAGBs is safe and maintains weight loss. Although a significant risk of future operative intervention remains, this can be reduced via the creation of a de novo retrogastric tunnel for band resiting.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BinWJD

GSE90594 Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signaling pathways

Contributors : L Michel ; P Reygagne ; P Benech ; F Jean-Louis ; S Scalvino ; S Ly Ka So ; Z Hamidou ; S Bianovici ; J Pouch ; B Ducos ; M Bonnet ; A Bensussan ; A Patatian ; E Lati ; J Wdzieczak-Bakala ; J C Choulot ; E Loing ; M Hocquaux
Series Type : Expression profiling by array
Organism : Homo sapiens

Background: The male androgenetic alopecia (AGA) is the most common form of hair loss in men and is hereditary in more than 80% of cases and characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be identified. Objectives: Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp skin vertex biopsies of hairless/bold men with premature AGA and healthy volunteers. Results: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory and immunoglobulin-associated immune mediators were significantly over-expressed in AGA. In contrast, under-expressed genes appear to be associated with the Wnt/β-catenin and BMP/TGF-β signaling pathways. Although the involvement of these pathways in hair follicle regeneration is well-described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin (POMC), as confirmed by RT-qPCR and immunohistochemistry. In addition, a lower expression of CYP27B1 in AGA patients supports that alteration of vitamin D metabolism contributes to hair loss. Conclusion: Altogether, this study provides evidence for distinct molecular events contributing to alopecia that might be targeted for new therapeutic approaches.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ymEWJr

GSE64811 Gene expression profiling of resident microglia and invading macrophages

Contributors : Golo Kronenberg ; Ria Uhlemann ; Karen Gertz
Series Type : Expression profiling by array
Organism : Mus musculus

Microglia represent the resident immune cells of the central nervous system. However, blood-borne monocytic cells are also able to invade the ischemic brain. In this study, we aim to characterize similarities and differences between these two cell populations using gene expression profiling.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ABSsPe

Nonalcoholic fatty liver disease in patients with psoriasis: A consequence of systemic inflammatory burden?

Abstract

Patients with psoriasis are at an increased risk for nonalcoholic fatty liver disease (NAFLD) compared to the general population. However, the pathophysiology underlying this comorbidity and elucidation of effective treatment strategies are unclear. This review provides insights into the possible role of chronic, low-grade inflammation in the pathogenesis of NAFLD in patients with psoriasis. Both conditions are associated with increased levels of pro-inflammatory adipokines (such as tumor necrosis factor-α and interleukin-6), and hepatokines, and decreased levels of adiponectin, an anti-inflammatory adipokine. This imbalance in inflammatory mediators could result in insulin resistance and, thereby, facilitate the occurrence and progression of NAFLD in a multistep manner. All patients with psoriasis should, therefore, be considered candidates for NAFLD screening and managed accordingly. Given the common etiology of inflammation between these conditions, it is hypothesized that biologic therapies for psoriasis may attenuate the systemic inflammatory process and progression of NAFLD in patients with psoriasis.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2iX6FLd

An observer blinded randomised controlled pilot trial comparing localised immersion psoralen ultraviolet A (PUVA) with localised narrowband ultraviolet B (NBUVB) for the treatment of palmar hand eczema

Summary

Background

Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Symptoms such as pain, itch and localised swelling contribute to disruption of activities of daily living, lack of sleep, and missed days from work. The aetiology is often multifactorial. Previous studies comparing psoralen ultraviolet A (PUVA) and narrowband ultraviolet B (NBUVB) have been small, non-randomised and retrospective.

Objectives

To conduct an observer blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NBUVB for the treatment of chronic hand eczema unresponsive to topical steroids.

Methods

60 patients (22 male, 38 female), median age 50 years (range 22, 73), with hand eczema unresponsive to clobetasol propionate 0.05% (Dermovate^®) (25 (42%) severe), were randomised to receive either immersion PUVA (n=30) or NBUVB (n=30) twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving a 'clear' or 'almost clear' Physician's Global Assessment (PGA) treatment response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI).

Results

In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, 5 patients achieved 'clear', and 8 'almost clear' (ITT response rate 43% (95%CI: 26%, 61%)). In the NB-UVB group, 2 achieved 'clear' and 5 'almost clear' (ITT response rate 23% (95%CI: 8%, 38%)). For the secondary outcomes, median (IQR) mTLSS scores were similar between groups at baseline (PUVA 9.5 (6.8,11), NBUVB 9 (6.8,12)) and at 12-weeks (PUVA 3 (1,6), NBUVB 4(2,8)). Changes in DLQI were similar with improvements in both groups.

Conclusions

In this randomised pilot trial recruitment was challenging. Once randomised, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems; PGA, mTLSS and DLQI as measures of treatment response, the trial demonstrated that both PUVA and NBUVB improved the severity of chronic palmar hand eczema. The study was not designed to demonstrate superiority of one treatment and a larger adequately powered RCT will be required to investigate this.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2BitN1r

CRISPR gene editing moved into humans in 2017

Scientists edited viable human embryos with CRISPR/Cas9 this year.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2nWKpGT

The Larsen C ice shelf break has sparked groundbreaking research

The hubbub over the iceberg that broke off Larsen C may have died down, but scientists are just getting warmed up to study the aftermath.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2Cb0iwb

The story of humans’ origins got a revision in 2017

Human evolution may have involved the gradual assembly of scattered skeletal traits, fossils of Homo naledi and other species show.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ASwcO3

Seven Earth-sized planets entered the spotlight this year

The discovery of seven Earth-sized planets orbiting a single cool star fuels a debate over what counts as good news in the search for life outside the solar system.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2C1gSxP

A quantum communications satellite proved its potential in 2017

Quantum communication through space is now possible, putting the quantum internet within closer reach.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2AUJwkP

Approval of gene therapies for two blood cancers led to an ‘explosion of interest’ in 2017

The first gene therapies approved in the United States are treating patients with certain types of leukemia and lymphoma.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ASw9ll

Brains of former football players showed how common traumatic brain injuries might be

Examinations of NFL players' postmortem brains turned up chronic traumatic encephalopathy in 99 percent of samples in large dataset.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2CaMKRo

Zika cases are down, but researchers prepare for the virus’s return

The number of Zika cases in the Western Hemisphere have dropped this year, but the need for basic scientific and public health research of the virus remains strong.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2nVmAPs

PI3Kδ activates E2F1 synthesis in response to mRNA translation stress

PI3Kδ activates E2F1 synthesis in response to mRNA translation stress

PI3Kδ activates E2F1 synthesis in response to mRNA translation stress, Published online: 13 December 2017; doi:10.1038/s41467-017-02282-w

The oncogenic activity of EBNA1 protein is unknown; it contains a glycine and alanine repeat sequence (GAr) which regulates its own translation in cis. Here the authors show that GAr stimulates PI3Kδ-mediated induction of E2F1 translation, leading to c-Myc induction and stimulation of proliferation.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ylNkbP

Atmospheric pressure mass spectrometric imaging of live hippocampal tissue slices with subcellular spatial resolution

Atmospheric pressure mass spectrometric imaging of live hippocampal tissue slices with subcellular spatial resolution

Atmospheric pressure mass spectrometric imaging of live hippocampal tissue slices with subcellular spatial resolution, Published online: 13 December 2017; doi:10.1038/s41467-017-02216-6

Ambient mass spectrometry-based approaches have found application in biology and medicine. Here the authors report a mass spectrometric imaging method (ambient nanoPALDI) for live hippocampal tissues, based on gold nanorodassisted femtosecond laser desorption and subsequent non-thermal plasma induced ionization.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2ym7wKS

In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering

In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering

In situ functional dissection of RNA <i>cis</i>-regulatory elements by multiplex CRISPR-Cas9 genome engineering, Published online: 13 December 2017; doi:10.1038/s41467-017-00686-2

RNA regulatory elements (RREs) are important post-transcriptional control features but studying them requires disrupting their activity without disturbing cellular homeostasis. Here the authors present GenERA, a CRISPR-Cas9 screening platform of in situ analysis of native RREs.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2Aza51V

A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases

A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases

A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases, Published online: 13 December 2017; doi:10.1038/s41467-017-02310-9

Bacteria adapt to changing environmental conditions through signal transduction mediated by the two-component system (TCS). Here, the authors combine X-ray crystallography and NMR studies to characterize a pH-gated conformational switch that regulates the phosphatase activity of TCS bifunctional histidine kinases.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2AB9woE

SYK kinase mediates brown fat differentiation and activation

SYK kinase mediates brown fat differentiation and activation

SYK kinase mediates brown fat differentiation and activation, Published online: 13 December 2017; doi:10.1038/s41467-017-02162-3

Spleen protein tyrosine kinase (Syk) has so far been mainly studied in haematopoietic and immune cells. Here, the authors show that Syk also has a role in brown adipose tissue, where it regulates the formation of brown adipocytes and their thermogenic activation in response to β-adrenergic stimulation.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2AyirHb

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