Using the Nursing Interventions Classification to identify nursing interventions in free-text nursing documentation in adult psychiatric outpatient care setting.

Abstract:
AIMS AND OBJECTIVES
To identify and describe nursing interventions in patient documentation in adult psychiatric outpatient setting and to explore the potential for using the Nursing Interventions Classification in documentation in this setting.

BACKGROUND
Documentation is an important part of nurses' work, and in the psychiatric outpatient care setting, it can be time-consuming. Only very few research reports are available on nursing documentation in this care setting.

METHODS
A qualitative analysis of secondary data consisting of nursing documentation for 79 patients in four outpatient units (years 2016-2017). The data consisted of 1,150 free-text entries describing a contact or an attempted contact with 79 patients, their family members or supporting networks and 17 nursing care summaries. Deductive and inductive content analysis was used. SRQR guideline was used for reporting.

RESULTS
We identified 71 different nursing interventions, 64 of which are described in the Nursing Interventions Classification. Surveillance and Care Coordination were the most common interventions. The analysis revealed two perspectives which challenge the use of the classification: the problem of overlapping interventions and the difficulty of naming group-based interventions.

CONCLUSION
There is an urgent need to improve patient documentation in the adult psychiatric outpatient care setting, and standardised nursing terminologies such as the Nursing Interventions Classification could be a solution to this. However, the problems of overlapping interventions and naming group-based interventions suggest that the classification needs to be further developed before it can fully support the systematic documentation of nursing interventions in the psychiatric outpatient care setting.

RELEVANCE TO CLINICAL PRACTICE
This study describes possibilities of using a systematic nursing language to describe the interventions nurses use in the adult psychiatric outpatient setting. It also describes problems in the current free text-based documentation.

Nursing Interventions Classification
outpatients
standardised nursing terminology
nursing records
psychiatric nursing


Evidence for interaction between the triheme cytochrome PpcA from Geobacter sulfurreducens and anthrahydroquinone-2,6-disulfonate, an analog of the redox active components of humic substances.

Abstract: The bacterium Geobacter sulfurreducens displays an extraordinary respiratory versatility underpinning the diversity of electron donors and acceptors that can be used to sustain anaerobic growth. Remarkably, G. sulfurreducens can also use as electron donors the reduced forms of some acceptors, such as the humic substance analog anthraquinone-2,6-disulfonate (AQDS), a feature that confers environmentally competitive advantages to the organism. Using UV-visible and stopped-flow kinetic measurements we demonstrate that there is electron exchange between the triheme cytochrome PpcA from Gs and AQDS. 2D-(1)H-(15)N HSQC NMR spectra were recorded for (15)N-enriched PpcA samples, in the absence and presence of AQDS. Chemical shift perturbation measurements, at increasing concentration of AQDS, were used to probe the interaction region and to measure the binding affinity of the PpcA-AQDS complex. The perturbations on the NMR signals corresponding to the PpcA backbone NH and heme substituents showed that the region around heme IV interacts with AQDS through the formation of a complex with a definite life time in the NMR time scale. The comparison of the NMR data obtained for PpcA in the presence and absence of AQDS showed that the interaction is reversible. Overall, this study provides for the first time a clear illustration of the formation of an electron transfer complex between AQDS and a G. sulfurreducens triheme cytochrome, shedding light on the electron transfer pathways underlying the microbial oxidation of humics.

Dantas|Joana M|JM|
Morgado|Leonor|L|
Catarino|Teresa|T|
Kokhan|Oleksandr|O|
Pokkuluri|P Raj|PR|
Salgueiro|Carlos A|CA|

Geobacter
Humics
AQDS
NMR
Electron transfer
Multiheme cytochromes


Dual mode competitive electrochemical immunoassay for B-type natriuretic peptide based on GS/SnO2/polyaniline-Au and ZnCo2O4/N-CNTs.

Abstract: A sensitive dual mode competitive electrochemical immunosensor for the detection of B-type natriuretic peptide (BNP) was successfully fabricated, which based on differential pulse voltammetry (DPV) and amperometric i-t curve response modes. Polyaniline (PAN) and tin dioxide (SnO2) were loaded on graphene sheets (GS), which could effectively promote the electron transfer process, thereby amplifying the current signal and increasing the sensitivity of the immunosensor. To promote biocompatibility, gold nanoparticles (Au) were incorporated on GS/SnO2/PAN (GS/SnO2/PAN-Au). GS/SnO2/PAN-Au complex was gotten to act as the platform which could provide a clearly DPV signals. N-doped carbon nanotubes (N-CNTs) embellished by ZnCo2O4 quantum dots (ZnCo2O4/N-CNTs) with excellent catalytic properties for the reduction of H2O2 was gotten to act as the label of the antibody-BNP (Ab), providing an obviously current signal through amperometric i-t curve method. A large quantity of BNP could be stable loaded in the modified electrode via GS/SnO2/PAN-Au with excellent electrical conductivity and good biocompatibility, which could compete with target-BNP to combine Ab that labelled by ZnCo2O4/N-CNTs. Under the optimum conditions, the immunosensor exhibited remarkable analytical performance of a linear range from 0.01 pg/mL to 1 ng/mL with a detection limit of 3.4 fg/mL for quantitative detection of BNP (S/N = 3). This method was able to become a universal strategy for other biological detection.

Li|Xuan|X| Liu|Li|L| Dong|Xue|X| Zhao|Guanhui|G| Li|Yueyuan|Y| Miao|Juncong|J| Fang|Jinglong|J| Cui|Min|M| Wei|Qin|Q| Cao|Wei|W|


Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: A structured summary of a study protocol for an open-label randomized clinical trial.

Abstract:
OBJECTIVE
General: To assess the virucidal efficacy of povidone iodine (PVP-I) on COVID-19 virus located in the nasopharynx Specific: i. To evaluate the efficacy of povidone iodine (PVP-I) to removeCOVID-19 virus located in the nasopharynx ii. To assess the adverse events of PVP-I TRIAL DESIGN: This is a single-center, open-label randomized clinical trial with a 7-arm parallel-group design.

PARTICIPANTS
The study will be conducted at Dhaka Medical College Hospital, Dhaka, Bangladesh.

INCLUSION CRITERIA
All RT-PCR-confirmed COVID-19 cases aged between 15-90 years with symptoms for the past 4 days will be screened. Those who give informed consent, are willing to participate, and accept being randomized to any assigned group will also be considered for final inclusion.

EXCLUSION CRITERIA
Patients with known sensitivity to PVP-I aqueous antiseptic solution or any of its listed excipients or previously diagnosed thyroid disease or who had a history of chronic renal failure: stage ≥3 by estimated glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) or had acute renal failure (KDIGO ≥stage 2: creatinine ≥2 times from the baseline) or patients who required invasive or noninvasive ventilation or planned within the next 6 hours were considered for exclusion. Moreover, lactating or pregnant women will also be restricted to include here.

INTERVENTION AND COMPARATOR
This RCT consist of seven arms: Arm-1 (intervention group): will receive povidone iodine (PVP-I) nasal irrigation (NI) at a concentration of 0.4% Arm-2 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.5% Arm-3 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.6%. Arm-4 (intervention group): will receive PVP-I nasal spray (NS) at a concentration of 0.5%. Arm-5 (intervention group): will receive PVP-I nasal spray at a concentration of 0.6%. Arm-6 (placebo comparator group): will receive distilled water through NI Arm-7 (Placebo comparator group): will receive distilled water through NS The intervention arms will be compared to the placebo comparator arms. Other supportive and routine care will be the same in both groups.

MAIN OUTCOMES
The primary outcome is the proportion of cases that remain COVID-19 positive following the intervention. It will be assessed from 1 minutes to 15 minutes after the intervention. Any occurrence of adverse effects following the intervention will be documented as a secondary outcome.

RANDOMIZATION
The assignment to the study (intervention) or control (comparator) group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and consenting procedures.

BLINDING (MASKING)
This is an open-label clinical trial, and no blinding or masking will be performed.

NUMBERS TO BE RANDOMIZED (SAMPLE SIZE)
A total of 189 confirmed cases of COVID-19 will be randomized into seven groups. In each arm, a total of 27 participants will be recruited.

TRIAL STATUS
The current trial protocol is Version 1.5 from September 10, 2020. Recruitment began September 30, 2020 and is anticipated to be completed, including data analysis by February 28, 2021.

TRIAL REGISTRATION
The trial protocol has been registered in the ClinicalTrials.gov on September 16, 2020. NCT Identifier number: NCT04549376 .

FULL PROTOCOL
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

D017322:Clinical Trials, Phase II as Topic

D016032:Randomized Controlled Trials as Topic

Povidone Iodine
COVID-19
Protocol
Randomized clinical trial
Nasal Irrigation
Nasal spray
DMC


Overexpression of TC2N is associated with poor prognosis in gastric cancer.

Abstract: Background: Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC. Methods: We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot (WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N. Results: The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was evidently associated with poor overall survival and recurrence-free survival. Conclusions: Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.

Xu|Jianbo|J| Ou|Xinde|X| Li|Jin|J| Cai|Qinbo|Q| Sun|Kaiyu|K| Ye|Jingning|J| Peng|Jianjun|J|


Conductive hydrogel composed of 1,3,5-benzenetricarboxylic acid and Fe3+ used as enhanced electrochemical immunosensing substrate for tumor biomarker.

Abstract: In this work, a new conductive hydrogel was prepared by a simple cross-linking coordination method using 1,3,5-benzenetricarboxylic acid as the ligand and Fe3+ as the metal ion. The hydrogel film was formed on a glassy carbon electrode (GCE) by a drop coating method, which can dramatically facilitate the transport of electrons. A sensitive label-free electrochemical immunosensor was fabricated following electrodeposition of gold nanoparticles (AuNPs) on a hydrogel film and immobilization of an antibody. Neuron-specific enolase (NSE), a lung cancer biomarker, was used as the model analyte to be detected. The proposed immunosensor exhibited a wide linear detection range of 1pgmL-1 to 200ngmL-1 and a limit of detection of 0.26pgmL-1 (the ratio of signal to noise (S/N)=3). Moreover, the detection of NSE in human serum samples showed satisfactory accuracy compared with the data determined by enzyme-linked immunosorbent assay (ELISA), indicating good analytical performance of the immunoassay.

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

Conductive hydrogel
1,3,5-Benzenetricarboxylic acid
Tumor biomarker
Electrochemical immunosensor
Neuron-specific enolase
Iron ion


Ethical considerations in deep brain stimulation for psychiatric illness.

Abstract: Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation.

Grant|Ryan A|RA|
Halpern|Casey H|CH|
Baltuch|Gordon H|GH|
O'Reardon|John P|JP|
Caplan|Arthur|A|

D046690:Deep Brain Stimulation
D006801:Humans
D007258:Informed Consent
D001523:Mental Disorders
D012107:Research Design

Ethics
Deep brain stimulation
Psychiatric
Depression
Mood
OCD


Conceptual development of "at-homeness" despite illness and disease: a review.

Abstract: Only one empirical study, the one by Zingmark, Norberg and Sandman published in 1995, explicitly focuses on at-homeness, the feeling of being metaphorically at-home, as a particular aspect of wellness. However, other studies reveal aspects of at-homeness, but if or how such aspects of at-homeness are related to each other is unclear. For this reason, the aim was to review Scandinavian nursing research related to at-homeness in the context of wellness-illness in severe and long-term conditions in order to take a step towards conceptual clarification of "at-homeness." The review included interpretive studies related to severe and long-term illness conducted in Sweden: 10 original articles and 5 doctoral theses. "At-homeness" was found to be a contextually related meaning of wellness despite illness and disease embedded in the continuum of being metaphorically at-home and metaphorically homeless. This was characterized by three interrelated aspects and four processes: being safe through expanding-limiting experiences of illness and time, being connected through reunifying-detaching ways of relating, and being centred through recognition-non-recognition of oneself in the experience and others giving-withdrawing a place for oneself. This conceptualization is to be regarded as a step in conceptual clarification. Further empirical investigation and theoretical development of "at-homeness" are needed. The conceptualization will be a step of plausible significance for the evaluation of interventions aimed at enhancing wellness for people with severe long-term illness, such as the frail elderly, and people with chronic illness or palliative care needs.

Ohlén|Joakim|J| Ekman|Inger|I| Zingmark|Karin|K| Bolmsjö|Ingrid|I| Benzein|Eva|E|

D000223:Adaptation, Psychological
D001294:Attitude to Health
D002908:Chronic Disease
D003210:Concept Formation
D006801:Humans
D015399:Nursing Research
D013548:Sweden

At-homeness
wellness
concept development
home
literature review
well-being


Severity and frequency of restless legs syndrome in patients with familial Mediterranean fever.

Abstract:
OBJECTIVE
Restless legs syndrome (RLS) is a common sensory motor disorder. RLS an urge to move the extremities that may be accompanied by dysesthesias, and significantly affects quality of life of affected patients. The frequency of RLS is higher in different systemic inflammatory diseases. Familial Mediterranean fever (FMF) is an inherited inflammatory disease characterized by attacks of polyserositis, arthritis, and fever. The prevalence of RLS in patients with FMF is unknown. This study aimed to evaluate the prevalence rate of RLS in a sample of patients with FMF and compare this prevalence with that of a matched normal population.

METHOD
A total of 60 patients with FMF and 60 healthy controls were studied. All participants underwent a neurological examination. Diagnostic criteria as proposed by the International Restless Legs Syndrome Study Group (IRLSSG) were used to define RLS. The IRLSSG rating scale for the severity of RLS was applied to determine the severity of symptoms.

RESULTS
The prevalence of RLS was not significantly different between patients and controls. Although the mean International Restless Legs Syndrome Rating Scale (IRLSRS) scores tended to be higher in patients compared with controls, this difference was not significant. When each item of the severity scale was compared between the two groups, significantly higher scores were found in some items of the IRLSRS in patients with FMF compared with controls.

CONCLUSION
According to this result, RLS symptoms in patients with FMF were more frequent and lasted longer than those in controls.

Yılmaz|Samet|S|
Çiğdem|Burhanettin|B|
Gökçe|Şeyda Figül|ŞF|
Ceyhan-Doğan|Sevil|S|
Balaban|Hatice|H|

restless legs syndrome
Familial Mediterranean fever
association


Oligo-anovulation is not a rarer feature in women with documented endometriosis.

Abstract:
OBJECTIVE
To study the prevalence of oligo-anovulation in women suffering from endometriosis compared to that of women without endometriosis.

DESIGN
A single-center, cross-sectional study.

SETTING
University hospital-based research center.

PATIENT (S)
We included 354 women with histologically proven endometriosis and 474 women in whom endometriosis was surgically ruled out between 2004 and 2016.

INTERVENTION
None.

MAIN OUTCOME MEASURE(S)
Frequency of oligo-anovulation in women with endometriosis as compared to that prevailing in the disease-free reference group.

RESULTS
There was no difference in the rate of oligo-anovulation between women with endometriosis (15.0%) and the reference group (11.2%). Regarding the endometriosis phenotype, oligo-anovulation was reported in 12 (18.2%) superficial peritoneal endometriosis, 12 (10.6%) ovarian endometrioma, and 29 (16.6%) deep infiltrating endometriosis.

CONCLUSION(S)
Endometriosis should not be discounted in women presenting with oligo-anovulation.

Santulli|Pietro|P|
Tran|Chloe|C|
Gayet|Vanessa|V|
Bourdon|Mathilde|M|
Maignien|Chloe|C|
Marcellin|Louis|L|
Pocate-Cheriet|Khaled|K|
Chapron|Charles|C|
de Ziegler|Dominique|D|

oligo-anovulation
Endometriosis
deep infiltrating endometriosis
antimüllerian hormone


Clinical utility of scores on the Blaylock Risk Assessment Screen (BRASS): An analysis of administrative data.

Abstract:
PURPOSE
Project was undertaken to examine the utility of the Blaylock Risk Assessment Screen (BRASS) in identifying patients who may experience discharge complications as indicated by longer hospital stays or readmission within 30-days of a discharge to home.

BACKGROUND
Before measures can be put in place to facilitate discharge planning and to prevent unplanned readmission by recently discharged patients, those at risk of such events must be identified.

METHODS
Project involved an analysis of 13-months of administrative data from one tertiary care hospital. Utility of the BRASS was examined in terms of its sensitivity and specificity as well as its positive and negative predictive values.

RESULTS
Majority (83%) of hospital discharges were to home. Approximately 7% of patients experienced at least one readmission within 30-days of being discharged to home. Using scores of 10 or higher as an indicator of risk, BRASS exhibited a high degree of specificity suggesting it is useful for 'ruling in' those who have the outcomes-of-interest. However low sensitivity indicates many who experienced the outcomes were incorrectly classified by the BRASS as low risk. The low positive predictive value for 30-day readmission also suggests many who were classified by the BRASS as being 'at risk' were not readmitted.

CONCLUSION
The observed rate of 30-day readmission is likely conservative as the analysis involved data from only one acute care facility. One explanation for the low positive predictive value for 30-day readmission is that completion of the BRASS on admission enabled the implementation of preventive measures.

Hodgins|Marilyn J|MJ|
Logan|Susan M|SM|
Fraser|Jacqueline M|JM|
Buck|Dawn-Marie|DM|
Stack|Bridget D|BD|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D005260:Female
D017408:Guidelines as Topic
D006801:Humans
D007902:Length of Stay
D008297:Male
D008875:Middle Aged
D010351:Patient Discharge
D010359:Patient Readmission
D011237:Predictive Value of Tests
D018570:Risk Assessment
D012307:Risk Factors
D012680:Sensitivity and Specificity
D062606:Tertiary Care Centers
D055815:Young Adult

Risk assessment
Length of stay
Patient readmission


A model to standardize safety and quality of care for cupping therapy.

Abstract: Cupping therapy has historical, traditional and religious value. It is increasingly popular in the field of complementary, alternative and integrative medicine. However, standards for safety and quality of service are absent. Although it is generally considered safe, cupping therapy can cause adverse events. Most of these events are predictable and preventable. A comprehensive approach to patient eligibility and therapist selection, along with compliance with standard operational procedures is essential to regulate the safety of the practice. Here we discuss a model framework for standardizing safety and quality of care. We recommend that this model be used routinely by cupping therapists and their associations on a nation-wide scale.

D000079742:Cupping Therapy
D006801:Humans
D011787:Quality of Health Care

Safety
Cupping therapy
Practice management
Theoretical models


Impact of Late Oseltamivir Treatment on Influenza Symptoms in the Outpatient Setting: Results of a Randomized Trial.

Abstract: We conducted a double-blind, randomized trial of 134 outpatients with polymerase chain reaction-confirmed influenza to assess the effects of oseltamivir initiated 48-119 hours after illness onset. Oseltamivir treatment did not reduce illness duration, severity, or duration of virus detection. However, the power of this study was limited due to lower than expected enrollment.

McLean|Huong Q|HQ|
Belongia|Edward A|EA|
Kieke|Burney A|BA|
Meece|Jennifer K|JK|
Fry|Alicia M|AM|


Unraveling the mysteries of modern size exclusion chromatography - the way to achieve confident characterization of therapeutic proteins.

Abstract: Modern size exclusion chromatography (SEC) can be defined by the use of relatively small columns (e.g., 150 × 4.6 mm) packed with sub-3 μm particles, allowing a 3- to 5-fold increase in method throughput compared to that of conventional SEC. The quick success of the first sub-2 μm SEC column introduced in 2010 led to the development of numerous ultra-high performance (UHP)-SEC columns for the analysis of therapeutic monoclonal antibody (mAb)-based products. Aggregates also known as high-molecular-weight species (HMWS) are indeed one of the most important critical quality attributes (CQAs) of mAbs, as HMWS may decrease the product efficacy or cause immunogenicity effects. Therefore, the confident characterization of mAbs requires strong knowledge of not only modern SEC performance (i.e., selectivity and efficiency) but also the inherent limitations caused by non-specific interactions more likely to occur with complex antibody drug conjugates (ADCs) and some commercial mAb products. This review discusses the importance of liquid chromatographic (LC) instrumentation in order to exploit the full potential of modern SEC columns and current trends to hyphenate SEC to mass spectrometry (MS). Recent applications for antibody-based products (i.e., mAbs, ADCs, Fc-Fusion proteins and bispecific antibodies) are presented. Finally, tips and tricks are provided to further optimize SEC separations and maintaining their performance over time with better understanding of unexpected SEC results.

Goyon|Alexandre|A| Fekete|Szabolcs|S| Beck|Alain|A| Veuthey|Jean-Luc|JL| Guillarme|Davy|D|

D018033:Antibodies, Bispecific
D000911:Antibodies, Monoclonal
D002850:Chromatography, Gel
D018796:Immunoconjugates
D013058:Mass Spectrometry
D011993:Recombinant Fusion Proteins

Size exclusion chromatography
Monoclonal antibody
Aggregate
Antibody drug conjugate
Bispecific antibody
Biopharmaceutical
Fusion proteins


Clinical, Structural, and Neuropathological Features of Olfactory Dysfunction in Patients with Alzheimer's Disease.

Abstract: We explored changes in clinical features and neuropathological mechanisms underlying olfactory dysfunction (OD) in 60 patients with Alzheimer's disease (AD). Olfactory function was evaluated using the Sniffin' Sticks test and a threshold discrimination identification (TDI) score. Based on the TDI score, we divided patients according to the presence or absence of OD (AD-OD and AD-NOD, respectively). Cognitive and neuropsychiatric symptoms were evaluated by a series of rating scales. The volumes and cortical thickness of the thalamus, hippocampus, and amygdala were measured using structural magnetic resonance imaging. Neuropathological protein levels in cerebrospinal fluid were measured. The frequency of OD was 50%. TDI scores were lower in the AD-OD group than in the AD-NOD group (p < 0.001). Compared with the AD-NOD group, the AD-OD group showed greater cognitive function impairments (p < 0.001), and daily living activities were more severely compromised (p = 0.019). The AD-OD group had lower hippocampal and amygdala volumes (p = 0.025, p = 0.030, respectively) and a more pronounced reduction in cortical thickness (p = 0.010). The total tau level was lower in the AD-OD group than the AD-NOD group (p = 0.040). Lower Mini-Mental State Examination scores and thinner AD-signature cortices were associated with lower TDI scores (OR = 0.826, p < 0.001; OR = 1.433, p = 0.008). Overall, in AD patients, the impairments in olfactory discrimination and identification seem to be more correlated with cognitive levels. OD in AD may be an indicator of pathological cognitive decline and structural changes.

Lian|Teng-Hong|TH| Zhu|Wan-Lin|WL| Li|Shao-Wu|SW| Liu|Ya-Ou|YO| Guo|Peng|P| Zuo|Li-Jun|LJ| Hu|Yang|Y| Yu|Shu-Yang|SY| Li|Li-Xia|LX| Jin|Zhao|Z| Yu|Qiu-Jin|QJ| Wang|Rui-Dan|RD| Zhang|Wei|W|

olfactory dysfunctions
clinical features
neuropathological mechanism
Alzheimer’s disease
structural MRI


Calcium-independent phospholipase A2γ enhances activation of the ATF6 transcription factor during endoplasmic reticulum stress.

Abstract: Injury of visceral glomerular epithelial cells (GECs) causes proteinuria in many glomerular diseases. We reported previously that calcium-independent phospholipase A2γ (iPLA2γ) is cytoprotective against complement-mediated GEC injury. Because iPLA2γ is localized at the endoplasmic reticulum (ER), this study addressed whether the cytoprotective effect of iPLA2γ involves the ER stress unfolded protein response (UPR). In cultured rat GECs, overexpression of the full-length iPLA2γ, but not a mutant iPLA2γ that fails to associate with the ER, augmented tunicamycin-induced activation of activating transcription factor-6 (ATF6) and induction of the ER chaperones, glucose-regulated protein 94 (GRP94) and glucose-regulated protein 78 (GRP78). Augmented responses were inhibited by the iPLA2γ inhibitor, (R)-bromoenol lactone, but not by the cyclooxygenase inhibitor, indomethacin. Tunicamycin-induced cytotoxicity was reduced in GECs expressing iPLA2γ, and the cytoprotection was reversed by dominant-negative ATF6. GECs from iPLA2γ knock-out mice showed blunted ATF6 activation and chaperone up-regulation in response to tunicamycin. Unlike ATF6, the two other UPR pathways, i.e. inositol-requiring enzyme 1α and protein kinase RNA-like ER kinase pathways, were not affected by iPLA2γ. Thus, in GECs, iPLA2γ amplified activation of the ATF6 pathway of the UPR, resulting in up-regulation of ER chaperones and cytoprotection. These effects were dependent on iPLA2γ catalytic activity and association with the ER but not on prostanoids. Modulating iPLA2γ activity may provide opportunities for pharmacological intervention in glomerular diseases associated with ER stress.

Elimam|Hanan|H|
Papillon|Joan|J|
Takano|Tomoko|T|
Cybulsky|Andrey V|AV|

D051702:Activating Transcription Factor 6

D000091342:Endoplasmic Reticulum Chaperone BiP

D020133:Reverse Transcriptase Polymerase Chain Reaction

Endoplasmic Reticulum Stress (ER Stress)


Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease: the ABSORB cohort A trial.

Abstract:
OBJECTIVES
This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California).

BACKGROUND
Multimodality imaging of the first-in-humans trial using a ABSORB BVS scaffold demonstrated at 2 years the bioresorption of the device while preventing restenosis. However, the long-term safety and efficacy of this therapy remain to be documented.

METHODS
In the ABSORB cohort A trial (ABSORB Clinical Investigation, Cohort A [ABSORB A] Everolimus-Eluting Coronary Stent System Clinical Investigation), 30 patients with a single de novo coronary artery lesion were treated with the fully resorbable everolimus-eluting Absorb scaffold at 4 centers. As an optional investigation in 3 of the 4 centers, the patients underwent multislice computed tomography (MSCT) angiography at 18 months and 5 years. Acquired MSCT data were analyzed at an independent core laboratory (Cardialysis, Rotterdam, the Netherlands) for quantitative analysis of lumen dimensions and was further processed for calculation of fractional flow reserve (FFR) at another independent core laboratory (Heart Flow, Redwood City, California).

RESULTS
Five-year clinical follow-up is available for 29 patients. One patient withdrew consent after 6 months, but the vital status of this patient remains available. At 46 days, 1 patient experienced a single episode of chest pain and underwent a target lesion revascularization with a slight troponin increase after the procedure. At 5 years, the ischemia-driven major adverse cardiac event rate of 3.4% remained unchanged. Clopidogrel was discontinued in all but 1 patient. Scaffold thrombosis was not observed in any patient. Two noncardiac deaths were reported, 1 caused by duodenal perforation and the other from Hodgkin's disease. At 5 years, 18 patients underwent MSCT angiography. All scaffolds were patent, with a median minimal lumen area of 3.25 mm(2) (interquartile range: 2.20 to 4.30). Noninvasive FFR analysis was feasible in 13 of 18 scans, which yielded a median distal FFR of 0.86 (interquartile range: 0.82 to 0.94).

CONCLUSIONS
The low event rate at 5 years suggests sustained safety after the implantation of a fully bioresorbable Absorb everolimus-eluting scaffold. Noninvasive assessment of the coronary artery with an option of functional assessment could be an alternative to invasive imaging after treatment of coronary narrowing with such a polymeric bioresorbable scaffold. (ABSORB Clinical Investigation, Cohort A [ABSORB A] Everolimus-Eluting Coronary Stent System Clinical Investigation [ABSORB]; NCT00300131).

Onuma|Yoshinobu|Y|
Dudek|Dariusz|D|
Thuesen|Leif|L|
Webster|Mark|M|
Nieman|Koen|K|
Garcia-Garcia|Hector M|HM|
Ormiston|John A|JA|
Serruys|Patrick W|PW|

D053805:Fractional Flow Reserve, Myocardial

noninvasive fractional flow reserve according to multislice computed tomography

P P P P P P P P P U M U U U U U U U U U U U U U M U M R M M U R M


Prevalence and Prognostic Value of Psychological Stress Events in Patients with First Myocardial Infarction-Long-Term Follow-Up Study.

Abstract: While there is good evidence that symptoms of depression determine prognosis of patients with coronary heart disease (CHD), the role of psychological stress is less clear. We evaluated the prognostic value of stressful events in patients with initial myocardial infarction (MI) with respect to subsequent cardiovascular events. The KAROLA-study included patients with CHD who participated in an in-patient rehabilitation program. A total of 577 patients with initial MI were included and self-reported psychological stressful events before their MI was assessed by a structured questionnaire. Hazard ratios were used to evaluate the long-term association of stressful events with secondary cardiovascular events. Additionally, associations of stressful events with depression, anxiety and other cardiovascular risk factors were investigated. Unusual stress at work (26.5%) and sleep disorder (23.4%) were the most frequently reported stressful events that occurred in the last 4 weeks before MI. However, only death of a family member showed a statistically significant increase in risk for subsequent cardiovascular events (HR: 1.59; 95%-CI: 1.01-2.50) and this result was not corrected for multiple testing. Notably, we found higher symptom scores of anxiety and depression associated with all single stressful event items. In conclusion, we found no clear patterns that psychological stressful events before MI would increase the long-term risk of subsequent adverse CHD events directly. However, we saw increased symptom scores of anxiety and depression in persons with stressful events.

psychological stress events
depression
coronary heart disease
myocardial infarction
anxiety


Dexamethasone sodium phosphate attenuates lipopolysaccharide-induced neuroinflammation in microglia BV2 cells.

Abstract: Abnormal neuroinflammation ignited by overproduction of chemokines and cytokines via microglial cells can induce the occurrence and development of neurodegenerative disorders. The aim of this study is to investigate the effects of dexamethasone sodium phosphate (Dex-SP) on chemokine and cytokine secretion in lipopolysaccharide (LPS)-activated microglial cells. LPS markedly enhanced the secretion of pro-inflammatory factors such as regulated on activation, normal T cell expressed and secreted (RANTES), transforming growth factor beta-β1 (TGF-β1) and nitric oxide (NO), but decreased the production of macrophage inflammatory protein-1α (MIP-1α) and interleukin 10 (IL-10) in BV-2 microglial cells. Furthermore, LPS increased BV-2 microglial cell migration. However, Dex-SP treatment had the opposite effect, dampening the secretion of RANTES, TGF-β1, and NO, while increasing the production of MIP-1α and IL-10 and blocking migration of LPS-stimulated BV-2 microglial cells. Furthermore, Dex-SP markedly suppressed the LPS-induced degradation of IRAK-1 and IRAK-4, and blocked the activation in TRAF6, p-TAK1, and p-JNK in BV-2 microglial cells. These results showed that Dex-SP inhibited the neuroinflammatory response and migration in LPS-activated BV-2 microglia by inhibiting the secretion of RANTES, TGF-β1, and NO and increasing the production of MIP-1α and IL-10. The molecular mechanism of Dex-SP may be associated with inhibition of TRAF6/TAK-1/JNK signaling pathways mediated by IRAK-1 and IRAK-4.

Hui|Bin|B| Yao|Xin|X| Zhang|Liping|L| Zhou|Qinhua|Q|

D048031:JNK Mitogen-Activated Protein Kinases

D048029:TNF Receptor-Associated Factor 6

Dexamethasone sodium phosphate
Microglia
Chemokine
Cytokine
LPS


Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: a randomized double-blind clinical trial.

Abstract:
BACKGROUND AND OBJECTIVE
The biochemical effects of an over-the-counter (OTC) medication were studied, which consists of a single-tuft brush containing cetylpyridinium chloride as a bactericidal agent, dipotassium glycyrrhizate as an anti-inflammatory drug and allantoin as a promoter of cell proliferation and wound healing, for delivery to hardly brushed sites.

MATERIAL AND METHODS
This randomized controlled double-blind study was performed in 61 subjects with chronic periodontitis in supportive periodontal therapy phase (test group: n = 27; placebo group: n = 28; dropout: n = 6). The OTC medication was self-applied twice a day for 12 wk to two molars with probing pocket depths of 4-6 mm. Biochemical indicators were evaluated at baseline and 12 wk using the suspension array system for eight cytokines and chemokines (interleukin [IL]-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor [TNF]-α) in gingival crevicular fluid.

RESULTS
The levels of IL-1β, IL-6, IL-8 and TNF-α remained significantly lower in the test group compared to the placebo group. In the placebo group, when the probing pocket depth at baseline was 4 mm, IL-1β increased, particularly in the second molar tooth, and the greatest increase was seen when PPD at baseline was 5-6 mm. In the test group, IL-1β decreased markedly in cases with furcation involvement and low bleeding on probing at baseline. In both groups, IL-1β, IL-6 and TNF-α were closely correlated with each other.

CONCLUSION
This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.

Takeuchi-Hatanaka|K|K| Yasuda|T|T| Naruishi|K|K| Katsuragi-Fuke|K|K| Inubushi|J|J| Ootsuki|H|H| Maeda|H|H| Takashiba|S|S|

D053590:Interleukin 1 Receptor Antagonist Protein

supportive periodontal therapy
inflammatory cytokine
over-the-counter medication
self-medication


Comparative Analysis of the Regulatory T Cells Dynamics in Peripheral Blood in Human and Porcine Polytrauma.

Abstract:
Background
Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma.

Methods
Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127-, and CD4+CD25+CD127-FoxP3+ were characterized by flow cytometry.

Results
Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127-), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain.

Conclusion
Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127- was characterized in porcine samples.

Serve|Rafael|R|
Sturm|Ramona|R|
Schimunek|Lukas|L|
Störmann|Philipp|P|
Heftrig|David|D|
Teuben|Michel P J|MPJ|
Oppermann|Elsie|E|
Horst|Klemens|K|
Pfeifer|Roman|R|
Simon|Tim P|TP|
Kalbas|Yannik|Y|
Pape|Hans-Christoph|HC|
Hildebrand|Frank|F|
Marzi|Ingo|I|
Relja|Borna|B|

regulatory T cell
porcine
polytrauma
lymphocyte
pig


Supplementary motor area connectivity and dual-task walking variability in multiple sclerosis.

Abstract:
BACKGROUND
Despite the prevalence of dual-task (e.g., walking while talking) deficits in people with multiple sclerosis (MS), no neuroimaging studies to date have examined neuronal networks used for dual-task processing or specific brain areas related to dual-task performance in this population. A better understanding of the relationship among underlying brain areas and dual-task performance may improve targeted rehabilitation programs. The objective of this study was to examine relationships between neuroimaging measures and clinical measures of dual-task performance, and reported falls in persons with MS.

MATERIALS AND METHODS
All participants completed measures of dual-task performance, a fall history, and neuroimaging on a 3 T MRI scanner. Spearman correlations were used to examine relationships among dual-task performance, falls and neuroimaging measures.

RESULTS
Eighteen females with relapsing-remitting MS [mean age = 45.5 ± 8.2 SD; mean symptom duration = 12.3 ± 6.7 years; Expanded Disability Status Scale median 2.25 (range 1.5-4)] participated in this study. Structural imaging measures of supplementary motor area (SMA) interhemispheric connectivity were significantly related to dual-task walking variability.

CONCLUSIONS
The SMA interhemispheric tract may play a role in dual-task performance. Structural neuroimaging may be a useful adjunct to clinical measures to predict performance and provide information about recovery patterns in MS. Functional recovery can be challenging to objectively report in MS; diffusion tensor imaging could show microstructural improvements and suggest improved connectivity.

Fritz|Nora E|NE|
Kloos|Anne D|AD|
Kegelmeyer|Deborah A|DA|
Kaur|Parminder|P|
Nichols-Larsen|Deborah S|DS|

Supplementary motor area
Dual-task
Walking
Multiple sclerosis
Neuroimaging


Activation of NLRP3 Inflammasome by Palmitic Acid in Human Sebocytes.

Abstract:
Background
Sebocytes are the main cells involved in the pathogenesis of acne by producing lipids and inflammatory cytokines. Although palmitic acid (PA) has been suggested to induce an inflammatory reaction, its effect on sebocytes remains to be elucidated.

Objective
In the present study, we investigated whether PA promotes inflammasome-mediated inflammation of sebocytes both in vivo and in vitro.

Methods
We intradermally injected PA into the mice ears. And, we treated cultured human sebocytes with PA. Inflammasome-mediated inflammation was verified by immunohistochemistry, Western blot and ELISA.

Results
PA-treated mice developed an inflammatory response associated with increased interleukin (IL)-1β expression in the sebaceous glands. When PA was added to cultured human sebocytes, caspase-1 activation and IL-1β secretion were significantly enhanced. In addition, NLRP3 knockdown attenuated IL-1β production by sebocytes stimulated with PA. PA-mediated inflammasome activation required reactive oxygen species.

Conclusion
These findings indicate that PA activates the NLRP3 inflammasome before induction of an inflammatory response in sebocytes. Thus, PA may play a role in the inflammation of acne.

NLRP3
Inflammasomes
Palmitic acid
Sebocyte


Can admission serum cystatin C level be an early marker subclinical acute kidney injury in critical care patients?

Abstract:
BACKGROUND
In critical care patients, the diagnosis of subclinical acute kidney injury (AKI) might be difficult with measurements of serum creatinine and estimated glomerular filtration rate (eGFR). Their 'sensitive kidneys' can easily be affected from sepsis, underlying diseases, medications and volume status and if they can be detected earlier, some preventive measures might be taken. In this study we aimed to determine whether admission serum cystatin C (sCys-C) and other clinical parameters can identify subclinical AKI in medical intensive care unit (ICU) patients with normal creatinine-based eGFR at admission.

METHODS
A prospective cohort study, performed in an adult ICU of a university hospital between January 2008 and March 2013. The blood samples were obtained within the first 24-48 hours of admission and sCys-C levels were analyzed with particle-enhanced immunonephelometric assay. AKI development was assessed according to RIFLE criteria. The cutoff value of sCys-C for the prediction of AKI was determined with receiver operating characteristic (ROC) curve analysis.

RESULTS
A total of 72 patients were included in the study and 19 (26%) of them developed AKI. Among the patients with AKI admission sCys-C levels were significantly higher when compared with non-AKI patients (1.06 ± 0.29 vs. 0.89 ± 0.28 respectively, p = 0.026). With ROC curve analysis, the threshold level for sCys-C was 0.94 mg/L with 63% sensitivity and 66% specificity [AUC: 0.67, p = 0.026]. With logistic regression analysis 'high sCys-C levels at admission' (OR = 4.73; 95%CI 1.03-21.5, p = 0.044) was found as one of the independent variables for the prediction of AKI development, in addition to 'being intubated before ICU admission' (OR = 10.2; 95%CI 1.72-60.4, p = 0.01) and 'hypotension during ICU follow-up' (OR = 12.3; 95%CI 2.5-60.1, p = 0.002).

CONCLUSION
In this cohort of patients, a high sCys-C level at admission was found to be a predictor of subclinical AKI arising during their ICU stay. If supported with further studies, it might be used to provide more accurate and earlier knowledge about renal dysfunction and to take appropriate preventive measures.

Gaygısız|Ümmügülsüm|Ü| Aydoğdu|Müge|M| Badoğlu|Melike|M| Boyacı|Nazlıhan|N| Güllü|Zuhal|Z| Gürsel|Gül|G|

Serum cystatin C
acute kidney injury
serum creatinine
glomerular filtration rate
intensive care unit


Naloxone rescheduling in Australia: Processes, implementation and challenges with supply of naloxone as a 'pharmacist only' over-the-counter medicine.

Abstract:
ISSUES
Numerous studies and systematic reviews have concluded that naloxone for take-home use is an effective intervention to reduce overdose morbidity and mortality, with few side effects and no abuse potential. One barrier to supply is that naloxone has traditionally been a prescription medication. In May 2015, the Therapeutic Goods Administration of Australia announced the intention to down-schedule naloxone when used for the treatment of opioid overdose, enabling sale in pharmacies without a prescription. The aim of this article is to describe process of rescheduling of naloxone and some of the challenges observed.

APPROACH
We describe the process of rescheduling from initial proposal development to gaining support and submissions from a range of individuals and professional bodies to support this change. The implications of the change, particularly for pharmacy supply of naloxone, are discussed, including next steps to facilitate implementation of this change in the Australian context.

KEY FINDINGS
A submission to reschedule naloxone was successfully instigated by a member of the public. The change may help remove access barriers to naloxone by allowing pharmacist supply. Cost, pharmacist training, existing naloxone formulation, presentation and packaging remain challenges to address.

IMPLICATIONS AND CONCLUSION
Naloxone down-scheduling has opened up an additional way to supply naloxone through community pharmacy. Further expansion of naloxone availability may be achieved through addressing cost as a barrier, and making naloxone more widely accessible through needle syringe programs, and other services that do not have medical staff.

naloxone rescheduling overdose pharmacy prevention


Rapid identification of efavirenz metabolites in rats and humans by ultra high performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry.

Abstract: An in vivo study of efavirenz metabolites in rats and human patients with ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry combined with MetabolitePilot(MT) software is reported for the first time. Considering the polarity differences between the metabolites, solid-phase extraction and protein precipitation were both applied as a part of the sample preparation method. The structures of the metabolites and their fragment ions were identified or tentatively characterized based on the accurate mass and MS(2) data. As a result, a total of 15 metabolites, including 11 from rat samples and 13 from human samples, were identified or tentatively characterized. Two metabolites and several new metabolism pathways are reported for the first time. This study provides a practical approach for identifying complicated metabolites through the rapid and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry technique, which could be widely used for the investigation of drug metabolites.

Deng|Yachen|Y| Liu|Rong|R| Yang|Ping|P| Liang|Jianying|J|

D002851:Chromatography, High Pressure Liquid

Efavirenz
High-resolution mass spectrometry
Human urine
Metabolite identification
Rat urine


Tumor-derived exosomal microRNAs and proteins as modulators of macrophage function.

Abstract: Tumor cells are able to modify their surrounding microenvironment by transmitting bioactive molecules via exosomes. In exosomes, proteins and nucleic acids that can be taken up by surrounding cells have been identified and modulate their functions. Tumor microenvironment consists of different cells such as macrophages. Tumors-associated macrophages (TAMs) express M2 phenotype and affect many processes including tumor initiation, angiogenesis, and metastasis. It has been demonstrated that a high number of TAMs is associated with poor prognosis of cancers. The contents of tumor-derived exosomes such as microRNAs and proteins induce macrophages to M2-like polarization to support tumor growth. Herein, we review the most recent studies on the effect of tumor-derived exosomes on macrophage polarization and function in different types of cancers.

D015972:Gene Expression Regulation, Neoplastic

tumor-derived exosomes
tumor microenvironment
tumors-associated macrophages
miRNAs


Optimal relief for pain at the end of life: a caregiver's tale.

Abstract: The current opioid crisis-driven partly by medical overprescription and partly by illegal drug abuse-is a significant cultural and professional dilemma in the USA and elsewhere. It has produced a strong reaction in favour of restricting medical use of opioids for pain, especially chronic pain. The author for a quarter century has written about pain from a biocultural perspective, and in this essay-based on his experience as primary caregiver for his late wife-he approaches the question of appropriate opioid use at the end of life.

D000701:Analgesics, Opioid
D001291:Attitude of Health Personnel
D017028:Caregivers
D059350:Chronic Pain
D003695:Delivery of Health Care
D006801:Humans
D009293:Opioid-Related Disorders
D059408:Pain Management
D010166:Palliative Care
D018454:Spouses
D013727:Terminal Care

care of the elderly
end-of-life care
medical humanities
narrative medicine
pain management


Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients.

Abstract: It is very necessary for patients with liver cancer to reasonably apply the prediction method of liver failure after hepatectomy before liver surgery. Liver surgeons can benefit greatly from clinical activities.

Liu|Yu|Y| Chen|Zheng-Liang|ZL| Yu|Xing-Xin|XX| Liang|Ying-Jian|YJ|

D006498:Hepatectomy
D048550:Hepatic Insufficiency
D006801:Humans
D017093:Liver Failure
D008113:Liver Neoplasms
D012307:Risk Factors


Clinical features of long-term low-dose levetiracetam treatment for epilepsy.

Abstract:
BACKGROUND
The aim of this study was to assess the rate of response to long-term low-dose levetiracetam (LEV) treatment and the clinical factors associated with response.

METHODS
The response to low-dose LEV of 43 patients with epilepsy (22 male, 21 female; age range, 5-39 years; median age, 13 years) was retrospectively assessed. Patients aged <15 years received <20 mg/kg/day LEV, whereas those aged ≥15 years received <1000 mg/day LEV. Clinical features were compared between responders to low-dose LEV, responders to the recommended dose, and non-responders.

RESULTS
Of the 43 patients who received low-dose LEV, 13 (30%) showed improvement, defined as seizure cessation or >75% seizure reduction over 6 months for patients with monthly, weekly, and daily seizures; and over 1 year for patients with yearly seizures. Efficacy was maintained for >1 year in 10 (77%) of the 13 patients. Long-term response to low-dose LEV was significantly associated with older age at onset and fewer previous treatments with ineffective anti-epileptic drugs. All patients showing long-term response to low-dose LEV developed only focal seizures.

CONCLUSIONS
Titration of LEV starting from a low dose may be effective in selected patients. Once patients respond to low-dose treatment, maintenance of the effective dosage may prolong response.

Yoshikawa|Sosuke|S| Shimakawa|Shuichi|S| Fukui|Miho|M| Nomura|Shohei|S| Tanabe|Takuya|T| Tamai|Hiroshi|H|

levetiracetam
epilepsy
titration
low-dose treatment
long-term treatment


Sputum cytokine mapping reveals an 'IL-5, IL-17A, IL-25-high' pattern associated with poorly controlled asthma.

Abstract:
BACKGROUND AND OBJECTIVE
Asthma is a heterogeneous disease with various clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA expression patterns in an unselected group of adult asthma patients to characterize the underlying inflammatory process.

METHODS
Differential cell counts and cytokine mRNA (quantified by real-time PCR) were analysed on sputum from 40 controls and 66 asthmatic adults. A 'cytokine-high' profile was defined if mRNA levels for that particular cytokine exceeded the 90th percentile value in the control population. Radar graphs were used to visualize cytokine profiles.

RESULTS
Sputum mRNA analysis confirmed heterogeneity of cytokine patterns among patients. Thirty-six patients (55%) had a Th2 cytokine pattern: 'IL-5-high' (n = 13), 'IL-4-high' (n = 17) or 'IL-4- and IL-5-high' (n = 6). The 'IL-5-high' asthma profile (n = 13) coincided with the 'IL-25-high' (10/13) and surprisingly also with the 'IL-17A-high' (11/13) profile. The 'IL-5-/IL-25-/IL-17A-high profile was different from the 'IL-4-high' pattern. Patients with the 'IL-5, IL-17A, IL-25-high' pattern had significantly worse lung function parameters. Uncontrolled asthmatics [Asthma Control Test (ACT) < 20] had higher sputum IL-5, IL-17A and IL-25 mRNA levels compared to controlled asthmatics (P = 0.002; P = 0.002; P = 0.066) and uncontrolled asthma is more common among 'IL-5- and IL-17A-high' asthmatics compared to 'IL-5-, IL-17A-low' asthmatics (χ(2) = 3.7, P = 0.027; relative risk (RR): 1.8, 95% CI = 1.1-3.1).

CONCLUSIONS AND CLINICAL RELEVANCE
Patients with the 'IL-5, IL-17A, IL-25-high' airway inflammatory pattern are often uncontrolled asthmatics, despite daily treatment. It seems worthwhile to evaluate whether measuring sputum cytokine levels might be used to assess the response to increased doses of steroids in patients with asthma.

Seys|S F|SF|
Grabowski|M|M|
Adriaensen|W|W|
Decraene|A|A|
Dilissen|E|E|
Vanoirbeek|J A|JA|
Dupont|L J|LJ|
Ceuppens|J L|JL|
Bullens|D M A|DM|

cytokine
asthma control
airway inflammation
asthma phenotyping
induced sputum


B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.

Abstract: Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.

Scheid|Johannes F|JF|
Barnes|Christopher O|CO|
Eraslan|Basak|B|
Hudak|Andrew|A|
Keeffe|Jennifer R|JR|
Cosimi|Lisa A|LA|
Brown|Eric M|EM|
Muecksch|Frauke|F|
Weisblum|Yiska|Y|
Zhang|Shuting|S|
Delorey|Toni|T|
Woolley|Ann E|AE|
Ghantous|Fadi|F|
Park|Sung-Moo|SM|
Phillips|Devan|D|
Tusi|Betsabeh|B|
Huey-Tubman|Kathryn E|KE|
Cohen|Alexander A|AA|
Gnanapragasam|Priyanthi N P|PNP|
Rzasa|Kara|K|
Hatziioanno|Theodora|T|
Durney|Michael A|MA|
Gu|Xiebin|X|
Tada|Takuya|T|
Landau|Nathaniel R|NR|
West|Anthony P|AP|
Rozenblatt-Rosen|Orit|O|
Seaman|Michael S|MS|
Baden|Lindsey R|LR|
Graham|Daniel B|DB|
Deguine|Jacques|J|
Bieniasz|Paul D|PD|
Regev|Aviv|A|
Hung|Deborah|D|
Bjorkman|Pamela J|PJ|
Xavier|Ramnik J|RJ|

D000911:Antibodies, Monoclonal
D057134:Antibodies, Neutralizing
D000914:Antibodies, Viral
D000936:Antigen-Antibody Complex
D000937:Antigen-Antibody Reactions
D001402:B-Lymphocytes
D000086382:COVID-19
D020285:Cryoelectron Microscopy
D018360:Crystallography, X-Ray
D020869:Gene Expression Profiling
D006801:Humans
D007070:Immunoglobulin A
D007135:Immunoglobulin Variable Region
D000072417:Protein Domains
D055503:Protein Multimerization
D020836:Protein Structure, Quaternary
D000086402:SARS-CoV-2
D017423:Sequence Analysis, RNA
D064370:Spike Glycoprotein, Coronavirus

monoclonal antibodies
cryo-electron microscopy
COVID-19
SARS-CoV cross-neutralization
disordered CDRH3
memory B cells
single B cell genomics


Accumulation of Hydrocarbons by Maize (Zea mays L.) in Remediation of Soils Contaminated with Crude Oil.

Abstract: This study has investigated the use of screened maize for remediation of soil contaminated with crude oil. Pots experiment was carried out for 60 days by transplanting maize seedlings into spiked soils. The results showed that certain amount of crude oil in soil (≤2 147 mg·kg(-1)) could enhance the production of shoot biomass of maize. Higher concentration (6 373 mg·kg(-1)) did not significantly inhibit the growth of plant maize (including shoot and root). Analysis of plant shoot by GC-MS showed that low molecular weight polycyclic aromatic hydrocarbons (PAHs) were detected in maize tissues, but PAHs concentration in the plant did not increase with higher concentration of crude oil in soil. The reduction of total petroleum hydrocarbon in planted soil was up to 52.21-72.84%, while that of the corresponding controls was only 25.85-34.22% in two months. In addition, data from physiological and biochemical indexes demonstrated a favorable adaptability of maize to crude oil pollution stress. This study suggested that the use of maize (Zea mays L.) was a good choice for remediation of soil contaminated with petroleum within a certain range of concentrations.

Liao|Changjun|C| Xu|Wending|W| Lu|Guining|G| Liang|Xujun|X| Guo|Chuling|C| Yang|Chen|C| Dang|Zhi|Z|

Maize
soil contamination
crude oil
PAHs
phytoremediation


Aggregate risk score based on markers of inflammation, cell stress, and coagulation is an independent predictor of adverse cardiovascular outcomes.

Abstract:
OBJECTIVES
This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI).

BACKGROUND
Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways-high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels-would be a powerful predictor of death and MI.

METHODS
Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors.

RESULTS
Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p < 0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cutpoints. Compared with the group with a 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of patients with a score of 3 compared with 2.4% in 36.4% of patients with a score of 0. The C statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score.

CONCLUSIONS
An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD.

Eapen|Danny J|DJ|
Manocha|Pankaj|P|
Patel|Riyaz S|RS|
Hammadah|Muhammad|M|
Veledar|Emir|E|
Wassel|Christina|C|
Nanjundappa|Ravi A|RA|
Sikora|Sergey|S|
Malayter|Dylan|D|
Wilson|Peter W F|PW|
Sperling|Laurence|L|
Quyyumi|Arshed A|AA|
Epstein|Stephen E|SE|

D005338:Fibrin Fibrinogen Degradation Products

myocardial infarction
MI
biomarker
C-reactive protein
CRP
fibrin degradation product
fibrin degradation product
FDP
heat shock protein
heat shock protein 70
HSP70
coronary artery disease
CAD
net reclassification improvement
CABG
CVD
IDI
LVEF
NRI
cardiovascular disease
coronary artery bypass grafting
eGFR
estimated glomerular filtration rate
fibrin degradation products
integrated discrimination improvement
left ventricular ejection fraction

P P P P P P P P P P P P P P U U U U U R M U M P M U


Biotin: From Nutrition to Therapeutics.

Abstract: Although frank symptomatic biotin deficiency is rare, some evidence suggests that marginal biotin deficiency occurs spontaneously in a substantial proportion of women during normal human pregnancy and might confer an increased risk of birth defects. Herein I review 1) advances in assessing biotin status, including the relation between acylcarnitine excretion and biotin status; 2) recent studies of biotin status in pregnancy; 3) advances in understanding the role of biotin in gene expression and the potential roles of biotinylated proteins that are neither histones nor carboxylases; and 4) novel large-dose biotin supplementation as therapy for multiple sclerosis. The review concludes with a summary of recent studies that have reported potentially dangerous erroneous results in individuals consuming large amounts of biotin for measurements of various plasma hormones for common clinical assays that use streptavidin-biotin technology.

biotin
gene expression
multiple sclerosis
hormone assays
interference
nutritional supplements


Obesity and postoperative atrial fibrillation in patients undergoing cardiac surgery: Systematic review and meta-analysis.

Abstract:
INTRODUCTION
Post-operative atrial fibrillation (POAF) is one of the most common complications following cardiac surgery. However, it is unclear whether there is a relationship between obesity and POAF. We thus assessed all available evidence investigating the association between obesity and POAF, also considering any link between POAF and other post-operative conditions such as mortality, stroke, myocardial infarctions and respiratory complications.

METHODS
Five electronic databases were searched and relevant studies were identified. Data was extracted and meta-analyzed from the identified studies.

RESULTS
We found that obese patients had significantly higher odds of POAF when compared with non-obese patients (P=0.006). There was also significant heterogeneity among the identified studies. POAF when compared with no-POAF was associated with an increased risk of stroke (P<0.0001), 30-day mortality (P=0.005) and respiratory complications (P<0.00001). However, we found no significant link between POAF and myocardial infarctions (P=0.79).

CONCLUSIONS
Our findings suggest that obesity is associated with a moderately higher risk of POAF. While POAF is also associated with an increased incidence of stroke, 30-day mortality and respiratory complications, further studies must be conducted before conclusions can be made about the long-term outcomes.

Phan|Kevin|K|
Khuong|Jacqueline Nguyen|JN|
Xu|Joshua|J|
Kanagaratnam|Aran|A|
Yan|Tristan D|TD|

Obesity
Postoperative atrial fibrillation
Atrial fibrillation
AF
Body mass index


MOF-Templated Assembly Approach for Fe3 C Nanoparticles Encapsulated in Bamboo-Like N-Doped CNTs: Highly Efficient Oxygen Reduction under Acidic and Basic Conditions.

Abstract: Developing high-performance non-precious metal catalysts (NPMCs) for the oxygen-reduction reaction (ORR) is of critical importance for sustainable energy conversion. We report a novel NPMC consisting of iron carbide (Fe3 C) nanoparticles encapsulated in N-doped bamboo-like carbon nanotubes (b-NCNTs), synthesized by a new metal-organic framework (MOF)-templated assembly approach. The electrocatalyst exhibits excellent ORR activity in 0.1 m KOH (0.89 V at -1 mA cm-2 ) and in 0.5 m H2 SO4 (0.73 V at -1 mA cm-2 ) with a hydrogen peroxide yield of below 1 % in both electrolytes. Due to encapsulation of the Fe3 C nanoparticles inside porous b-NCNTs, the reported NPMC retains its high ORR activity after around 70 hours in both alkaline and acidic media.

oxygen-reduction reaction
iron carbides
metal-organic frameworks
heterogeneous catalysis
nanostructured materials


Untying the knot of transcription factor druggability: Molecular modeling study of FOXM1 inhibitors.

Abstract: The FOXM1 protein is a relevant transcription factor involved in cancer cell proliferation. The direct or indirect inhibition of this protein's transcriptional activity by small molecule drugs correlates well with a potentially significant anti-cancer profile, making this macro molecule a promising drug target. There are a few drug molecules reported to interact with (and inhibit) the FOXM1 DNA binding domain (FOXM1-BD), causing downregulation of protein expression and cancer cell proliferation inhibition. Among these drug molecules are the proteasome inhibitor thiostrepton, the former antidiabetic drug troglitazone, and the new FDI-6 molecule. Despite their structural differences, these drugs exert a similar inhibitory profile, and this observation prompted us to study a possible similar mechanism of action. Using a series of molecular dynamics simulations and docking protocols, we identified essential binding interactions exerted by all three classes of drugs, among which, a π-sulfur interaction (between a His287 and a sulfur-containing heterocycle) was the most important. In this report, we describe the preliminary evidence suggesting the presence of a drug-binding pocket within FOXM1 DNA binding domain, in which inhibitors fit to dissociate the protein-DNA complex. This finding suggests a common mechanism of action and a basic framework to design new FOXM1 inhibitors.

Tabatabaei-Dakhili|S Amirhossein|SA|
Aguayo-Ortiz|Rodrigo|R|
Domínguez|Laura|L|
Velázquez-Martínez|Carlos A|CA|

FOXM1 Thiostrepton Troglitazone Thiazolidinediones


Long noncoding RNA NEAT1 promotes cell proliferation, migration, and invasion in hepatocellular carcinoma through interacting with miR-384.

Abstract: It was reported that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR-384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR-384 exhibited the functions of tumor-suppressive. The expression of miR-384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR-384 expression, whereas inhibition of miR-384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR-384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA-binding protein immunoprecipitation assays. Overexpression of miR-384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR-384.

nuclear enriched abundant transcript 1 (NEAT1)


An expression for the bridge-mediated electron transfer rate in dye-sensitized solar cells.

Abstract: We have derived an expression for the rate of electron transfer between a semiconductor and a redox centre connected to the semiconductor via a molecular bridge. This model is particularly useful to study the charge recombination (CR) process in dye-sensitized solar cells, where the dye is often connected to the semiconductor by a conjugated bridge. This formalism, designed to be coupled with density functional theory electronic structure calculations, can be used to explore the effect of changing the bridge on the rate of interfacial electron transfer. As an example, we have evaluated the CR rate for a series of systems that differ in the bridge length.

electron transfer
dye-sensitized solar cell
interface
tunnelling


Clinical features of IgG4-related rhinosinusitis.

Abstract:
PURPOSE
IgG4-related disease is a systemic disease that affects various organs of the body. Aim of this study is to elucidate the clinical characteristics of IgG4-related rhinosinusitis.

MATERIAL AND METHODS
Clinical features, laboratory findings, radiological and endoscopic findings, associated disease, treatment and prognosis were retrospectively examined in 10 patients with IgG4-related rhinosinusitis.

RESULTS
The age was 59.1±11.3 years old and male-to-female ratio was 1:1. The chief nasal complaints were hyposmia (n=4), nasal obstruction (n=3), and nothing (n=3). Serum IgG4 levels were elevated in all patients and the value was 740.4±472.4mg/dl. Other IgG4-related diseases were associated in all 10 patients, including IgG4-related sialadenitis (n=6), IgG4-related dacryoadenitis (n=5), and autoimmune pancreatitis (n=5). Imaging findings on CT/MRI were obstruction of the way of elimination (n=10), thickening of the sinus mucous membrane (n=10), and fluid in the sinus (n=6). All of the cases had bilateral findings. Nasal endoscopic findings were chiefly deviated nasal septum (n=5), polyps (n=4), edema of the mucous membrane (n=3). Histologically, abundant infiltration of IgG4 positive plasma cell and lymphocyte and an elevated IgG4+/IgG+ cell ration was detected in all 8 patients and 5 patients, respectively. Endoscopic sinus surgery was performed in 8 patients. Eight patients were treated with steroid therapy for other associated IgG4-related diseases. Symptoms improved in all 6 patients after an initial treatment (endoscopic surgery (n=5) and steroids (n=1)), but one patient suffered relapse.

CONCLUSIONS
IgG4-related rhinosinusitis is a distinct entity of IgG4-related disease, and is associated in patients with multiple IgG4-related diseases.

Hanaoka|Machiko|M| Kammisawa|Terumi|T| Koizumi|Satomi|S| Kuruma|Sawako|S| Chiba|Kazuro|K| Kikuyama|Masataka|M| Shirakura|Satoshi|S| Sugimoto|Taro|T| Hishima|Tsunekazu|T|

Rhinosinusitis
IgG4-related disease
IgG4
Steroid


Concordance Between ICD-10 Codes and Clinical Diagnosis of Hypoparathyroidism in Sweden.

Abstract:
Introduction
Chronic hypoparathyroidism is a rare disorder. The disease is characterized by low serum calcium, high serum phosphate, and deficient production of parathyroid hormone. The most common etiology is unintentional damage and intentional removal to the parathyroid glands during anterior neck surgery. Other causes include genetic disorders and autoimmune diseases. Knowledge about the epidemiology of chronic hypoparathyroidism is sparse and the prevalence in Sweden is unknown. It is of importance to know the validity of the registers used to study the epidemiology of hypoparathyroidism in Sweden. The purpose of this study was to validate the International Classification of Diseases - 10th revision (ICD-10) diagnosis of hypoparathyroidism in the Swedish National Patient Register.

Methods
We included patients with the ICD-10 diagnosis of hypoparathyroidism that were found in the Swedish National Patient Register during 2004 to 2016. Through the unique national registration number assigned to all Swedish inhabitants, we could link this information to the Swedish Prescribed Drug Register. We included patients with an ICD-10 diagnosis for hypoparathyroidism and on concurrent conventional treatment for the disease. The validation of the diagnosis was assessed through review of medical records of 120 patients.

Results
A total of 958 patients, 70% women (n=671) and 30% men (n=287) met the inclusion criteria. In total, 120 randomly chosen medical records were reviewed and 109 cases were confirmed. This corresponds to an overall positive predictive value of 91%.

Conclusion
The validity of the ICD-10 diagnosis of hypoparathyroidism in the Swedish National Patient Register is high and the register is a reliable source for further research. There is a risk of miscoding when assigning an ICD-code to the medical records. We urge clinicians to be aware of this risk, especially the risk of mix-ups with the more common diagnosis of hyperparathyroidism.


Transcriptional Profiling Suggests T Cells Cluster around Neurons Injected with Toxoplasma gondii Proteins.

Abstract: Toxoplasma gondii's tropism for and persistence in the central nervous system (CNS) underlies the symptomatic disease that T. gondii causes in humans. Our recent work has shown that neurons are the primary CNS cell with which Toxoplasma interacts and which it infects in vivo This predilection for neurons suggests that T. gondii's persistence in the CNS depends specifically upon parasite manipulation of the host neurons. Yet, most work on T. gondii-host cell interactions has been done in vitro and in nonneuronal cells. We address this gap by utilizing our T. gondii-Cre system that allows permanent marking and tracking of neurons injected with parasite effector proteins in vivo Using laser capture microdissection (LCM) and RNA sequencing using RNA-seq, we isolated and transcriptionally profiled T. gondii-injected neurons (TINs), Bystander neurons (nearby non-T. gondii-injected neurons), and neurons from uninfected mice (controls). These profiles show that TIN transcriptomes significantly differ from the transcriptomes of Bystander and control neurons and that much of this difference is driven by increased levels of transcripts from immune cells, especially CD8+ T cells and monocytes. These data suggest that when we used LCM to isolate neurons from infected mice, we also picked up fragments of CD8+ T cells and monocytes clustering in extreme proximity around TINs and, to a lesser extent, Bystander neurons. In addition, we found that T. gondii transcripts were primarily found in the TIN transcriptome, not in the Bystander transcriptome. Collectively, these data suggest that, contrary to common perception, neurons that directly interact with or harbor parasites can be recognized by CD8+ T cells.IMPORTANCE Like other persistent intracellular pathogens, Toxoplasma gondii, a protozoan parasite, has evolved to evade the immune system and establish a chronic infection in specific cells and organs, including neurons in the CNS. Understanding T. gondii's persistence in neurons holds the potential to identify novel, curative drug targets. The work presented here offers new insights into the neuron-T. gondii interaction in vivo By transcriptionally profiling neurons manipulated by T. gondii, we unexpectedly revealed that immune cells, and specifically CD8+ T cells, appear to cluster around these neurons, suggesting that CD8+ T cells specifically recognize parasite-manipulated neurons. Such a possibility supports evidence from other labs that questions the long-standing dogma that neurons are often persistently infected because they are not directly recognized by immune cells such as CD8+ T cells. Collectively, these data suggest we reconsider the broader role of neurons in the context of infection and neuroinflammation.

Merritt|Emily F|EF|0000-0002-9449-4683
Johnson|Hannah J|HJ|
Wong|Zhee Sheen|ZS|
Buntzman|Adam S|AS|
Conklin|Austin C|AC|
Cabral|Carla M|CM|
Romanoski|Casey E|CE|
Boyle|Jon P|JP|
Koshy|Anita A|AA|0000-0001-8705-3233

Toxoplasma gondii
laser capture microdissection
RNA-seq
transcriptomics
host-pathogen interactions
immunology
neuroscience


Coexistence with Large Carnivores Informed by Community Ecology.

Abstract: Conserving predators on an increasingly crowded planet brings very difficult challenges. Here, we argue that community ecology theory can help conserve these species in human-dominated landscapes. Letting humans and predators share the same landscapes is similar to maintaining a community of predatory species, one of which is humans.

coexistence
large carnivores
community ecology
predators


Natural Alternatives for Chemicals Used in Histopathology Lab- A Literature Review.

Abstract: Histopathology lab is the place where the specimen gets processed and stained to view under microscope for interpretation. Exposure to the chemicals used in these processes cause various health hazards to the laboratory technicians, pathologists, and scientists working in the laboratory. Hence, there is a dire need to introduce healthy and bio-friendly alternatives in the field. This literature review explores the natural products and their efficiency to be used as alternatives for chemicals in the histopathology lab.

Ramamoorthy|Ananthalakshmi|A| Ravi|Shivani|S| Jeddy|Nadeem|N| Thangavelu|Radhika|R| Janardhanan|Sunitha|S|

Natural products
Occupational hazards
Pathology


Geriatric Conditions in Patients Undergoing Defibrillator Implantation for Prevention of Sudden Cardiac Death: Prevalence and Impact on Mortality.

Abstract:
BACKGROUND
Geriatric conditions may influence outcomes among patients receiving implantable cardioverter-defibrillators (ICDs). We sought to determine the prevalence of frailty and dementia among older adults receiving primary prevention ICDs and to determine the impact of multimorbidity on mortality within 1 year of ICD implantation.

METHODS AND RESULTS
The cohort included 83 792 Medicare patients from the National Cardiovascular Data Registry ICD Registry who underwent first primary prevention ICD implantation between 2006 and 2009. These data were merged with Medicare analytic files to determine the prevalence of frailty, dementia, and other conditions before ICD implantation, as well as 1-year mortality. A validated claim-based algorithm was used to identify frail patients. Mutually exclusive patterns of chronic conditions were examined. The association of each pattern with 1-year mortality was assessed using logistic regression models adjusted for selected patient characteristics. Approximately 1 in 10 Medicare patients with heart failure receiving a primary prevention ICD had frailty (10%) or dementia (1%). One-year mortality was 22% for patients with frailty, 27% for patients with dementia, and 12% in the overall cohort. Several multimorbidity patterns were associated with high 1-year mortality rates: dementia with frailty (29%), frailty with chronic obstructive pulmonary disease (25%), and frailty with diabetes mellitus (23%). These patterns were present in 8% of the cohort.

CONCLUSIONS
More than 10% of Medicare beneficiaries with heart failure receiving primary prevention ICDs have frailty or dementia. These patients had significantly higher 1-year mortality than those with other common chronic conditions. Frailty and dementia should be considered in clinical decision-making and guideline development.

Green|Ariel R|AR|
Leff|Bruce|B|
Wang|Yongfei|Y|
Spatz|Erica S|ES|
Masoudi|Frederick A|FA|
Peterson|Pamela N|PN|
Daugherty|Stacie L|SL|
Matlock|Daniel D|DD|

D029424:Pulmonary Disease, Chronic Obstructive

geriatrics
dementia
Medicare
defibrillators, implantable
pulmonary disease, chronic obstructive


Reduction of Salmonella Shedding by Sows during Gestation in Relation to Its Fecal Microbiome.

Abstract: Pork meat is estimated to be responsible for 10-20% of human salmonellosis cases in Europe. Control strategies at the farm could reduce contamination at the slaughterhouse. One of the targeted sectors of production is maternity, where sows could be Salmonella reservoirs. The aim of this study was to assess the dynamics of shedding of Salmonella in terms of variation in both shedding prevalence and strains excreted during gestation in Quebec's maternity sector. The evolution of the fecal microbiota of these sows during gestation was also assessed to detect bacterial populations associated with these variations. A total of 73 sows both at the beginning and the end of the gestation were randomly selected and their fecal matter was analyzed. Salmonella detection was conducted using a method that includes two selective enrichment media (MSRV and TBG). Nine isolates per positive samples were collected. Among the 73 sows tested, 27 were shedding Salmonella. Sows in the first third of their gestation shed Salmonella significantly more frequently (21/27) than those in the last third (6/46) (χ2P < 0.05). The shedding status of 19 of the sows that were previously sampled in the first third of their gestation was followed, this time in the last third of their gestation, which confirmed reduction of shedding. Using 16S rRNA gene sequencing and qPCR, significant differences between the fecal flora of sows at the beginning and the end of the gestation, shedding Salmonella or not and with different parity number were detected. Using MaAsLin, multiple OTUs were found to be associated with the time of gestation, the status of Salmonella excretion and parity number. Some of the identified taxa could be linked to the reduction of the shedding of Salmonella at the end of gestation. In this study, we showed that the level of Salmonella shedding was variable during gestation with significantly higher shedding at the beginning rather than at the end of gestation. We also observed for the first time a significant change in the microbiota during sow gestation and identified interesting taxa which could be linked to a reduced Salmonella shedding.

Larivière-Gauthier|Guillaume|G| Thibodeau|Alexandre|A| Letellier|Ann|A| Yergeau|Étienne|É| Fravalo|Philippe|P|

Salmonella
sows
gestation
excretion
fecal microbiota


Violent firearm-related conflicts among high-risk youth: An event-level and daily calendar analysis.

Abstract: Firearm homicide is the leading cause of violence-related youth mortality. To inform prevention efforts, we analyzed event-level data to identify unique precursors to firearm conflicts. Youth (ages:14-24) seeking Emergency Department (ED) treatment for assault or for other reasons and reporting past 6-month drug use were enrolled in a 2-year longitudinal study. Time-line follow-back substance use/aggression modules were administered at baseline and each 6-month follow-up. Violent non-partner conflicts were combined across time-points. Regression analyzed: a)antecedents of firearm-related conflicts (i.e., threats/use) as compared to non-firearm conflicts; and b)substance use on conflict (vs. non-conflict) days for those engaged in firearm conflict. During the 24-months, we found that 421-youth reported involvement in violent non-partner conflict (n=829-conflicts;197-firearm/632-non-firearm). Among firearm conflicts, 24.9% involved aggression and 92.9% involved victimization. Retaliation was the most common motivation for firearm-aggression (51.0%), while "shot for no reason" (29.5%) and conflicts motivated by arguments over "personal belongings" (24.0%) were most common for firearm-victimization. Male sex (AOR=5.14), Black race (AOR=2.75), a ED visit for assault (AOR=3.46), marijuana use before the conflict (AOR=2.02), and conflicts motivated by retaliation (AOR=4.57) or personal belongings (AOR=2.28) increased the odds that a conflict involved firearms. Alcohol (AOR=2.80), marijuana (AOR=1.63), and prescription drugs (AOR=4.06) had a higher association with conflict (vs. non-conflict) days among youth reporting firearm conflict. Overall, we found that firearm conflicts are differentially associated with substance use and violence motivations. Addressing substance use, interrupting the cycle of retaliatory violence, and developing conflict resolution strategies that address escalation over infringement on personal belongings may aid in decreasing and preventing adolescent firearm violence.

Carter|Patrick M|PM|
Walton|Maureen A|MA|
Goldstick|Jason|J|
Epstein-Ngo|Quyen M|QM|
Zimmerman|Marc A|MA|
Mercado|Melissa C|MC|
Williams|Amanda Garcia|AG|
Cunningham|Rebecca M|RM|

Daily calendar analysis
Firearm violence
Event-level analysis
Injury prevention


Prevalence and Clinical Implications of the Primitive Trigeminal Artery and its Variants: A Meta-Analysis.

Abstract:
BACKGROUND
The primitive trigeminal artery (PTA) is the most common and the largest persistent carotid-basilar anastomosis. Primitive trigeminal artery variants (PTAVs) are anastomoses between the internal carotid artery and cerebellar arteries. These vessels pose a risk of hemorrhagic or ischemic complications during neurosurgical procedures in the parasellar and intrasellar regions. The aim of this study was to determine the prevalence of both PTA and PTAVs and their clinically important anatomic features.

METHODS
Major electronic databases were thoroughly searched for studies on PTA and PTAV. References in the included articles were also evaluated. Data regarding prevalence, laterality, origin, course patterns, and associated anomalies were extracted and pooled into a meta-analysis.

RESULTS
A total of 39 studies (110,866 patients) were included in the meta-analysis. The total pooled prevalence estimate of PTA and PTAVs combined was 0.4% (95% confidence interval [CI], 0.3-0.5). Individually, PTA was present in 0.3% of patients and PTAV in 0.2%. Both arteries most often originated from the C4 internal carotid artery and took a course lateral to the dorsum sellae. The anterior inferior cerebellar artery type was the predominant PTAV (72.1%). Basilar artery hypoplasia was found in 42.5% of patients with a PTA.

CONCLUSIONS
PTA and PTAVs are rare vessels, but they are clinically important because they can contribute to trigeminal neuralgia. Knowledge of the potential course of these arteries is essential in neuroradiology and neurosurgery, especially in minimally invasive procedures such as the endoscopic endonasal transsphenoidal approach to the pituitary gland and the percutaneous gasserian ganglion procedure.

Brzegowy|Karolina|K|
Pękala|Przemysław A|PA|
Zarzecki|Michał P|MP|
Pękala|Jakub R|JR|
Roy|Joyeeta|J|
Aziz|Hasina M|HM|
Tubbs|R Shane|RS|
Walocha|Jerzy A|JA|
Tomaszewski|Krzysztof A|KA|
Mikos|Marcin|M|

D020785:Central Nervous System Vascular Malformations

Primitive trigeminal artery
Carotid-basilar anastomosis
Internal carotid artery
Fetal intracranial artery
Vascular anatomy


Transnasal endoscopic assisted dacryocystorhinostomy.

Abstract: Transnasal endoscopic dacryocystorhinostomy is a good alternative for external DCR. It is considered a safe and efficient technique with successful results, comparable or even better than the external technique. Advanced knowledge of the endoscopic anatomy and the lacrimal system is necessary to perform the procedure safely, and to obtain good surgical outcomes. The aim of the paper is to analyze the changes of the endoscopic technique and to improve it. The transnasal endoscopic dacryocystorhinostomy surgical technique is described in a "step by step" manner. Also the surgical technologies that can be used for this intervention are presented, focusing on the cold instruments.

Hainăroșie|Răzvan|R| Ioniță|Irina|I| Pietroșanu|Cătălina|C| Pițuru|Silviu|S| Hainăroșie|Mura|M| Zainea|Viorel|V|


High molecular weight hyaluronan for treatment of chronic shoulder pain associated with glenohumeral arthritis.

Abstract:
BACKGROUND
There is insufficient evidence to determine whether intra-articular injections may be effective for treatment of glenohumeral osteoarthritis. Euflexxa(®) (high molecular weight hyaluronate), a bioengineered high molecular weight hyaluronan, has been shown to be a safe and effective treatment for patients with knee osteoarthritis. There is also support for the use of hyaluronate injection for the treatment of chronic shoulder pain associated with osteoarthritis or rotator cuff damage. This small-scale exploratory study was conducted to evaluate the safety and efficacy of high molecular weight hyaluronate for the treatment of chronic shoulder pain associated with osteoarthritis.

METHODS
Subjects with glenohumeral osteoarthritis and chronic pain (n = 27) received one injection per week for 3 weeks of high molecular weight hyaluronate and were assessed for changes in pain (100 mm visual analog scale [VAS]), range of motion, and the subject's and physician's global assessment over 26 weeks. Subjects were also assessed for pain, stiffness, and physical functioning using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Finally, responses were evaluated using modified Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Proposition D criteria. Safety was assessed by recording adverse events.

RESULTS
High molecular weight hyaluronate significantly improved pain (VAS, WOMAC), range of motion, stiffness, and physical functioning scores; 77.8% of subjects were rated as having an OMERACT-OARSI Proposition D high response. There were no serious adverse events, and none were considered to be related to treatment.

CONCLUSION
Treatment with high molecular weight hyaluronate improves pain, stiffness, and range of motion, and may have an acceptable safety and tolerability profile. A randomized, double-blind, placebo-controlled clinical trial may be warranted to investigate further the efficacy and safety of intra-articular high molecular weight hyaluronate for treatment of chronic shoulder pain in patients with glenohumeral osteoarthritis.

hyaluronan
shoulder
pain
osteoarthritis
range of motion
Euflexxa®


Contributing factors in forceps associated pelvic floor trauma.

Abstract:
INTRODUCTION AND HYPOTHESIS
Levator avulsion occurs in 10-35% of women after a first vaginal delivery, with forceps being the main risk factor. Three mechanisms have been proposed to account for the high risk of trauma: the additional space requirement, increased speed of distension, and/ or greater force. This study examines the additional space requirements associated with forceps to determine any associated increase in avulsion risk.

METHODS
This was an in vitro simulation study of spatial requirements for delivery of a fetal head by forceps, with mathematical modelling of spatial requirements using data from a local observational study. A balloon device was used to model head circumferences through the range of expected measurements at term, with measurements taken after application of three different types of forceps. Each measurement was performed in triplicate.

RESULTS
On average, forceps increased the circumference of the fetal head by 1.01 cm for Wrigley's, 1.04 cm for Kielland's, and 1.64 cm for Neville-Barnes forceps, resulting in an estimated increase in the diameter of the fetal head by 0.32 cm, 0.33 cm, and 0.52 cm, respectively. This increase was linear throughout the tested range. In 534 singleton pregnancies at term, we determined an odds ratio (OR) of 1.11 per centimeter head circumference for avulsion. Hence, the additional space requirement due to forceps explains ORs of 1.11, 1.12, and 1.19 for avulsion, depending on forceps type.

CONCLUSIONS
The effect of forceps on avulsion risk is not fully explained by the increase in space requirement alone. Other factors, such as shortened time to maximum distension and/or increased peak force applied may contribute to the excess risk.

Forceps
Levator avulsion
Head circumference
Birth trauma
Pelvic organ prolapse


Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists.

Abstract: Liposomes are powerful tools for the optimization of peptides and adjuvant composition in cancer vaccines. Here, we take advantage of a liposomal platform versatility to develop three vaccine candidates associating a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant. Liposomal vaccine containing MPLA (TLR4 liposomes), are the most effective treatment against the HPV-transformed orthotopic lung tumor mouse model, TC-1. This vaccine induces a potent Th1-oriented antitumor immunity, which leads to a significant reduction in tumor growth and a prolonged survival of mice, even when injected after tumor appearance. This efficacy is dependent on CD8+ T cells. Subcutaneous injection of this treatment induces the migration of skin DCs to draining lymph nodes. Interestingly, TLR2/6 liposomes trigger a weaker Th1-immune response which is not sufficient for the induction of a prolonged antitumor activity. Although NOD1 liposome treatment results in the control of early tumor growth, it does not extend mice survival. Surprisingly, the antitumor activity of NOD1 vaccine is not associated with a specific adaptive immune response. This study shows that our modulable platform can be used for the strategical development of vaccines.

Jacoberger-Foissac|Célia|C| Saliba|Hanadi|H| Wantz|May|M| Seguin|Cendrine|C| Flacher|Vincent|V| Frisch|Benoît|B| Heurtault|Béatrice|B| Fournel|Sylvie|S|

D056704:Adaptive Immunity
D000818:Animals
D000970:Antineoplastic Agents
D018414:CD8-Positive T-Lymphocytes
D019496:Cancer Vaccines
D045744:Cell Line, Tumor
D049109:Cell Proliferation
D008081:Liposomes
D008175:Lung Neoplasms
D008297:Male
D051379:Mice
D008810:Mice, Inbred C57BL
D000070576:NLR Proteins
D010455:Peptides
D051193:Toll-Like Receptors

Toll-like and nod-like receptor agonists


Highly-efficient visible-light-driven photocatalytic H2 evolution integrated with microplastic degradation over MXene/ZnxCd1-xS photocatalyst.

Abstract: The development of highly-efficient photocatalyst for H2 production integrated with microplastic degradation is significant to meet the demand for clean energy and resolve "white pollution". Herein, a series of MXene/ZnxCd1-xS photocatalysts were successfully fabricated for H2 evolution integrated with degradation of polyethylene terephthalate (PET). The resultant photocatalysts exhibited excellent photocatalytic performance, and the best photocatalytic H2 evolution rate can reach 14.17 mmol·g-1·h-1 in alkaline PET alkaline solution. What's more, the PET was also converted to the useful organic micromolecule, including glycolate, acetate, ethanol, etc. The highly-efficient photocatalytic performance of MXene/ZnxCd1-xS photocatalysts can be attributed to the enhanced separation ability of photocarriers and optimum band structure with enhanced oxidation capacity of valence band. Finally, the photocatalytic mechanism was investigated in detail. Overall, this work supplied a new useful guidance for solving the energy problem and microplastic pollution issues, simultaneously.

Cao|Bingqian|B| Wan|Shipeng|S| Wang|Yanan|Y| Guo|Haiwei|H| Ou|Man|M| Zhong|Qin|Q|

Microplastic degradation
H(2) evolution
MXene/Zn(x)Cd(1-x)S
Mechanism analysis
Photocatalysis