Multiple cutaneous plasmacytosis with multilobated (clover-leaf shaped) nuclei cells in a dog.

Abstract: A 12-year-old female Shih-tzu dog was presented with a 2-month history of cutaneous non-pruritic multiple ulcerated or crusted nodules of less than 1.5 cm in diameter on eyelids, lips, abdomen, groin, thighs and perianal region. Several diagnostic tests were performed, including fine needle aspiration and skin biopsy of the cutaneous nodules. Cytologic interpretation was round cell neoplasm with multilobated (clover-leaf shaped) nuclei. Histopathology revealed round neoplastic cells with prominent anisocytosis and anisokaryosis, and numerous mitotic figures; however, the origin of the cells was not identified. Immunohistochemical evaluation indicated that these cells were positive for CD79a and MUM-1, but negative for CD3, CD20 and Pax 5. The patient was treated with chemotherapy, and the skin condition improved. Despite good response to chemotherapy, the patient was euthanized due to poor general health.

Lee|Jongbok|J|
Lee|Jung Keun|JK|
Kim|Jawon|J|
Choi|Ul Soo|US|
Seo|Kyoung Won|KW|0000-0002-1561-3278

cutaneous plasmacytosis
multilobated
clover-leaf shape
dog
cytology
plasmacytoma


BDNF Activates Postsynaptic TrkB Receptors to Induce Endocannabinoid Release and Inhibit Presynaptic Calcium Influx at a Calyx-Type Synapse.

Abstract: Brain-derived neurotropic factor (BDNF) has been shown to play critical roles in neural development, plasticity, and neurodegenerative diseases. The main function of BDNF in the brain is widely accepted to be synaptic regulation. However, how BDNF modulates synaptic transmission, especially the underlying signaling cascades between presynaptic and postsynaptic neurons, remains controversial. In the present study, we investigated the actions of BDNF at rat calyx-type synapses of either sex by measuring the excitatory postsynaptic current (EPSC) and presynaptic calcium current and capacitance changes. We found that BDNF inhibits the EPSC, presynaptic calcium influx, and exocytosis/endocytosis via activation of the presynaptic cannabinoid Type 1 receptors (CB1Rs). Inhibition of the CB1Rs abolished the BDNF-induced presynaptic inhibition, whereas CB1R agonist mimicked the effect of BDNF. Exploring the underlying signaling cascade, we found that BDNF specifically activates the postsynaptic TrkB receptors, inducing the release of endocannabinoids via the PLCγ/DGL pathway and retrogradely activating presynaptic CB1Rs. We also reported the involvement of AC/PKA in modulating vesicle endocytosis, which may account for the BDNF-induced calcium-dependent and -independent regulation of endocytosis. Thus, our study provides new insights into the BDNF/endocannabinoid-associated modulation of neurotransmission in physiological and pathologic processes.SIGNIFICANCE STATEMENT BDNF plays critical roles in the modulation of synaptic strength. However, how BDNF regulates synaptic transmission and its underlying signaling cascade(s) remains elusive. By measuring EPSC and the presynaptic calcium current and capacitance changes at rat calyces, we found that BDNF inhibits synaptic transmission via BDNF-TrkB-eCB signaling pathway. Activation of postsynaptic TrkB receptors induces endocannabinoid release via the PLCγ/DGL pathway, retrogradely activating the presynaptic CB1Rs, inhibiting the AC/PKA, and suppressing calcium influx. Our findings provide a comprehensive understanding of BDNF/endocannabinoid-associated modulation of neuronal activities.

Wu|Yichen|Y| Liu|Qingzhuo|Q| Guo|Bin|B| Ye|Fangfei|F| Ge|Jianlong|J| Xue|Lei|L|0000-0002-7601-3989

BDNF
endocannabinoid
exocytosis
endocytosis
AC/PKA
retrograde signaling


A novel vortex assisted dispersive solid phase extraction of some trace elements in essential oils and fish oil.

Abstract: In this paper, a novel vortex assisted solid phase extraction procedure combined with inductively coupled plasma optic emission spectrometry was presented for determination of Mn, Cu, Ni, Cr, Cd and Pb directly in oily matrix. The suggested separation and preconcentration method was based on simultaneous sorption of the target analytes from real essential oil matrix onto γ-Al2O3 functionalized with fluorescein (Al-Flr) and transfer to aqueous eluent prior to quantification. The effect of different parameters including sorption and elution time, sample volume, eluent type and concentration and interfering ions were investigated. The working conditions were given as follows, vortex agitation for sorption and elution 40 s, sample volume 20 mL, eluent type HCl, eluent concentration 0.3 mol L-1. The detection limits were found to be 0.7 μg L-1 for Mn, 4.1 μg L-1 for Cu, 1.0 μg L-1 for Ni, 1.6 μg L-1 for Cr, 0.7 μg L-1 Cd and 1.0 μg L-1 Pb. The evaluation of the accuracy and precision of the method was tested via metallo-organic certified reference material. The recovery values have warranted the accuracy and found between 98.4 and 103.3% with 2.6-6.4% relative standard deviation (RSD, %). The sampling frequency of the procedure was calculated as 11.25 h-1. Finally, the proposed analytical method was successfully applied on analyte spiked and unspiked apricot, black cumin, pine turpentine, thyme, mint essential oils and fish oil samples without any need of performing mineralization pretreatments.

D005395:Fish Oils
D009822:Oils, Volatile
D052616:Solid Phase Extraction
D014131:Trace Elements
D014874:Water Pollutants, Chemical

Dispersive solid phase extraction
Essential oil
Preconcentration
Alumina
ICP OES


Colorectal surgery in elderly population.

Abstract:
INTRODUCTION
With the rising number of elderly patients and increasing incidence of colorectal cancer, management of geriatric patients has become the forefront of colorectal surgery.

OBJECTIVES
This study aimed to investigate the short-term surgical outcomes following colorectal resection in elderly patients.

MATERIALS AND METHODS
A total of 464 patients who underwent surgical resection for colorectal tumor between 2013 and 2017 were included. The patients were divided into elderly (≥75 years) and young (<75 years) group. The clinicopathological data of the patients were reviewed retrospectively.

RESULTS
The elderly group constituted 30% of study population. More patients in elderly group underwent Hartmann procedure (p=0.02) and right hemicolectomy (p=0.029), and younger patients more often received low anterior resection (p=0.027). The surgical procedure took a shorter time in elderly group (p<0.01) but they stayed in the hospital one day longer (p=0.023). Postoperative complications and mortality tended to be higher in seniors (p=0.088). The younger patients showed a tendency towards a higher rate of distant metastases (p=0.053). Seniors received fewer preoperative chemoradiation than the young group (p=0.014).

CONCLUSION
Older persons constitute one-third of patients treated electively in colorectal departments. Colorectal surgery in geriatric patients is associated with a prolonged hospital stay and a higher potential for complications and mortality.

Zawadzki|Marek|M| Krzystek-Korpacka|Małgorzata|M| Rząca|Marek|M| Czarnecki|Roman|R| Obuszko|Zbigniew|Z| Witkiewicz|Wojciech|W|

D000367:Age Factors
D000368:Aged
D000369:Aged, 80 and over
D003110:Colonic Neoplasms
D015179:Colorectal Neoplasms
D003107:Colorectal Surgery
D005260:Female
D006801:Humans
D007902:Length of Stay
D008297:Male
D008875:Middle Aged
D011044:Poland
D011183:Postoperative Complications
D011184:Postoperative Period
D012189:Retrospective Studies
D012307:Risk Factors

colorectal surgery
elderly
colorectal cancer


Survival Impact of Adjuvant Chemotherapy for Resected Locally Advanced Rectal Adenocarcinoma.

Abstract:
BACKGROUND
Recent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy.

PATIENTS AND METHODS
This is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed.

RESULTS
A total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long-course chemoradiation followed by surgery. Four hundred fifty-two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine-based chemotherapy. At a median follow-up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five-year relapse-free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58-1.51; P = .780). No significant impact on relapse-free survival was seen for either pCR or non-pCR patients. Five-year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37-1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non-pCR subset of patients (HR, 0.49; 95% CI, 0.28-0.86; P = .014).

CONCLUSION
A high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5-year OS only in the patients with a non-pCR.

Tay|Rebecca Y|RY|
Jamnagerwalla|Murtaza|M|
Steel|Malcolm|M|
Wong|Hui-Li|HL|
McKendrick|Joseph J|JJ|
Faragher|Ian|I|
Kosmider|Suzanne|S|
Hastie|Ian|I|
Desai|Jayesh|J|
Tacey|Mark|M|
Gibbs|Peter|P|
Wong|Rachel|R|

D000971:Antineoplastic Combined Chemotherapy Protocols

Preoperative chemoradiotherapy
Pathologic complete response
Surgery
Overall survival
Postoperative chemotherapy


N-Myristoyltransferase 1 enhances human immunodeficiency virus replication through regulation of viral RNA expression level.

Abstract: N-myristoyltransferase (NMT) catalyzes protein N-myristoylation. It has been suggested that the isozyme NMT1 enhances the replication of human immunodeficiency virus type-1 (HIV-1). However, the details of the mechanism by which NMT1 does so remain unclear. In this study, we investigated NMT1-binding proteins by co-immunoprecipitation and mass spectrometry. As a result, several RNA-binding proteins including ribosomal proteins, NMT isozymes, and hnRNP A2/B1 were observed to bind to NMT1, as mediated mainly by RNA. Interestingly, only hRNP A2/B1 was found to associate with NMT1 without mediation by RNA. It was also suggested that hnRNP A2/B1 contributes to the formation of complexes of high molecular weights involving NMT1. Knockdown of hnRNP A2/B1 resulted in the enhancement of viral replication with an increase in the expression level of viral RNA in HIV-1-producing cells. On the other hand, knockdown of NMT1 resulted in the attenuation of viral replication with the decrease in the expression level of viral RNA in HIV-1-producing cells. Additionally, overexpression of NMT1 induced the enhancement of viral replication with the increase in the expression level of the viral RNA. These findings suggest that both NMT1 and hnRNP A2/B1 take part in the regulation of HIV-1 RNA expression through their mutual opposite effects on the viral RNA expression in HIV-1-producing cells.

Ohta|Hikaru|H| Takamune|Nobutoki|N| Kishimoto|Naoki|N| Shoji|Shozo|S| Misumi|Shogo|S|

D015967:Gene Expression Regulation, Viral

D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B

N-myristoyltransferase 1
RNA
HIV-1
HnRNP A2/B1


Cross-diagnostic scale-banking using rasch analysis: Developing a common reference metric for generic and health condition-specific scales in people with rheumatoid arthritis and stroke.

Abstract:
OBJECTIVES
To develop a common reference metric of functioning, incorporating generic and health condition-specific disability instruments, and to test whether this reference metric is invariant across 2 health conditions.

DESIGN
Psychometric study using secondary data analysis. Firstly, the International Classification of Functioning, Disability and Health (ICF) Linking Rules were used to examine the concept equivalence between the World Health Organization Disability Assessment Schedule (WHODAS 2.0), Health Assessment Questionnaire (HAQ) and Functional Independence Measure (FIMTM). Secondly, a scale-bank was developed using a reference metric approach to test-equating, based on the Rasch measurement model.

PARTICIPANTS
Secondary analysis was performed on data from 487 people; 61.4% with rheumatoid arthritis and 38.6% with stroke.

RESULTS
Three sub-domains of the WHODAS 2.0 and all items of the HAQ and FIMTM motor mapped on to the ICF chapters d4 Mobility, d5 Self-care and d6 Domestic life. Test-equating of these scales resulted in good model fit, indicating that a scale bank and associated reference metric across these 3 instruments could be created.

CONCLUSION
This study provides a transformation table to enable direct comparisons among instruments measuring physical functioning commonly used in rheumatoid arthritis (HAQ) and stroke (FIMTM motor scale), as well as in people with disability in general (WHODAS 2.0).

Prodinger|Birgit|B|
Küçükdeveci|Ayşe A|AA|
Kutlay|Sehim|S|
Elhan|Atilla H|AH|
Kreiner|Svend|S|
Tennant|Alan|A|


Novel design of smart sleep-lighting system for improving the sleep environment of children.

Abstract:
BACKGROUND
Children struggle to fall asleep by themselves because of their physiological characteristics. Therefore, research has been carried on various devices (such as a smartphone) to assist in improving the sleep quality of children. However, all such devices need to be controlled by parents and do not have functions for monitoring the sleep environment.

OBJECTIVE
In this paper, a smart sleep-lighting system that includes a sleep-lighting device and a smartphone dongle is developed to improve the sleep environment of children.

METHODS
The temperature, humidity, and luminance of the sleep environment are monitored and analyzed by the sleep-lighting device to control multi-color light and audio components. The colored light emitted by the multi-color light can be adjusted to improve the sleep atmosphere. Also, the audio component can play white noise to induce sleep. In addition, parents can use a smartphone dongle with a multi-channel wireless communication method to monitor and control one or more lighting devices in different locations in real time.

RESULTS
For environmental monitoring, average difference between proposed device and commercial sensor from chamber setting temperature 15∘C to 35∘C was 0.588∘C ± 0.10∘C, and average error value of the humidity measurement was 0.74% at 40% ∼ 60% RH. Also, the manufactured sleep-lighting device shows good performance in multi-color light emission, and playing of white noise. As result, the smartphone connected to the proposed smartphone dongle enables monitoring and control of the proposed lighting device in a wireless well.

CONCLUSIONS
The manufactured sleep-lighting device has a high-precision temperature and humidity sensor and a luminance sensor that can accurately monitor the sleeping environment. The lighting device can play white noise to induce sleep in children. Also, a multi-color LED light is operated via a smartphone application to improve the sleep atmosphere. The measured data will be sent to the lighting device and processed together with sleep environment data in order to improve the sleep quality. Additionally, the final system will be tested for real end-users with clinical experiments by sleep research center of a university hospital.

Wei|Qun|Q|
Lee|Jyung Hyun|JH|
Park|Hee-Joon|HJ|

sleep environment
Children
smartphone dongle
mood light
sleep aid
wireless multi-channel communication


Variability in Risk Assessment and Management Plan (RAMP) scores completed as part of the Ontario Johne's Education and Management Assistance Program(2010-2013).

Abstract: As a proactive measure toward controlling the nontreatable and contagious Johne's disease in cattle, the Ontario dairy industry launched the voluntary Ontario Johne's Education and Management Assistance Program in 2010. The objective of this study was to describe the results of the first 4 yr of the program and to investigate the variability in Risk Assessment and Management Plan (RAMP) scores associated with the county, veterinary clinic, and veterinarian. Of 4,158 Ontario dairy farms, 2,153 (51.8%) participated in the program between January 2010 and August 2013. For this study, RAMP scores and whole-herd milk or serum ELISA results were available from 2,103 farms. Herd-level ELISA-positive prevalence (herds with one or more test-positive cows were considered positive) was 27.2%. Linear mixed model analysis revealed that the greatest RAMP score variability was at the veterinarian level (24.2%), with relatively little variability at the county and veterinary clinic levels. Consequently, the annual RAMP should be done by the same veterinarian to avoid misleading or discouraging results.

Pieper|Laura|L|
DeVries|Trevor J|TJ|
Sorge|Ulrike S|US|
Godkin|Ann|A|
Hand|Karen J|KJ|
Perkins|Nicole R|NR|
Imada|Jamie|J|
Kelton|David F|DF|

D016927:Mycobacterium avium subsp. paratuberculosis

risk assessment
participation
control program
paratuberculosis


Analysis of Street-Crossing Behavior: Comparing a CAVE Simulator and a Head-Mounted Display among Younger and Older Adults.

Abstract: Interactive pedestrian simulators have become a valuable research tool for investigating street-crossing behavior and developing solutions for improving pedestrian safety. There are two main kinds of pedestrian simulators: one uses a technology based on rear-projection screens (Cave Automatic Virtual Environment, or CAVE), the other a head-mounted display (HMD). These devices are used indiscriminately, regardless of the research objective, and it is not yet known whether they are equally effective for studying street crossing. The present study was aimed at comparing the street crossing behavior and subjective evaluations of younger and older adult pedestrians when they are using a CAVE-like or HMD-based (HTC Vive Pro) pedestrian simulator. Thirty younger adults and 25 older adults performed 36 street-crossing trials (combining different speeds, two-way traffic conditions, and gap sizes) on each of the two types of simulators. The results indicated that participants in the HMD condition crossed the street significantly more often (58.6 %) than in the CAVE condition (42.44%) and had shorter safety margins. The most striking difference pertained to crossing initiation, which occurred considerably earlier (1.78 s) in the HMD condition than in the CAVE condition. Synchronization of crossing initiation with oncoming traffic was not as good in the CAVE condition because visual information in front of the pedestrian was missing due to the absence of ground projection. In both simulators, older adults caused more collisions than did younger ones, had shorter safety margins, and a slower crossing speed. Hence, the HMD reproduced classical age-related differences in most street-crossing behaviors already found on the CAVE. Usually observed speed effects were also found for both simulators. Neither cybersickness nor any adverse effects on stereoacuity or postural balance were found for either simulator. The HMD produced a higher level of presence and preference than the CAVE did. These findings provide evidence that HMDs have a clear potential for studying pedestrian behaviour.

Pala|Prashant|P|
Cavallo|Viola|V|
Dang|Nguyen Thong|NT|
Granié|Marie-Axelle|MA|
Schneider|Sonja|S|
Maruhn|Philipp|P|
Bengler|Klaus|K|

Street-crossing behavior
CAVE
head-mounted display (HMD)
aging
virtual reality


Nomenclatural and taxonomic updates in Rourea subgen. Rourea sect. Multifoliolatae (Connaraceae).

Abstract: The pantropical genus Rourea Aubl. (Connaraceae) is composed of ca. 70 species, most of which occur in the Neotropics. Rourea is currently subdivided into three subgenera, with the American taxa included in Rourea subgen. Rourea. Forero (1976) recognised six sections for the species of the New World, with Rourea subgen. R. sect. Multifoliolatae being exclusive to Brazil, characterised by multifoliolate leaves, relatively small leaflets and the staminal tube (0.8-)1-1.5 mm long. Following Forero's (1976) treatment, additional botanical collections have become available in Brazilian herbaria, allowing re-evaluation of species concepts. This work recognises and revises 12 species in this section, mainly restricted to southeastern Brazil and southern Bahia. A nomenclatural and taxonomic study of these species is here presented, including an identification key, morphological descriptions, illustrations and geographic distribution maps. A new species is also described.

Toledo|Cassio A P|CAP|
Souza|Vinicius Castro|VC|
Lucas|Eve J|EJ|

Brazil
new species
Oxalidales
Cnestideae
systematics
typification


Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway.

Abstract: CMTM3 (CKLF-like MARVEL transmembrane domain containing 3) possesses tumor suppressor properties in multiple types of malignancies. Restoration of CMTM3 significantly inhibits the metastasis of gastric cancer, and its expression level is correlated with prognosis. However, the physiological effects and the mechanism of CMTM3 remain unknown. Here, we suppress CMTM3 expression by shRNA to explore its endogenous effects and its mechanism of action in gastric cancer. Stable knockdown of CMTM3 promotes cell migration, invasion and tumor metastasis, increases MMP2 expression and enhances MMP2 activity. CMTM3 inhibits EMT along with the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin and Twist1. It has no obvious effects on Zeb1 and Snail. CMTM3 suppresses the phosphorylation of STAT3 but not Akt. More importantly, the EMT phenotype and cell migration induced by CMTM3 knockdown can be reversed by the Jak2/STAT3 inhibitor JSI-124 or by siRNA against STAT3 or Twist1. Overall, this study demonstrates that knockdown of CMTM3 promotes the metastasis of gastric cancer through the STAT3/Twist1/EMT pathway.

Yuan|Wanqiong|W| Li|Ting|T| Mo|Xiaoning|X| Wang|Xiaolin|X| Liu|Baocai|B| Wang|Wenyan|W| Su|Yu|Y| Xu|Lan|L| Han|Wenling|W|

D015972:Gene Expression Regulation, Neoplastic


Comparative analyses of ACE2 and TMPRSS2 gene: Implications for the risk to which vertebrate animals are susceptible to SARS-CoV-2.

Abstract: Along with the control and prevention of coronavirus disease 2019 transmission, infected animals might have potential to carry the virus to spark new outbreaks. However, very few studies explore the susceptibility of animals to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Viral attachment as a crucial step for cross-species infection requires angiotensin-converting enzyme 2 (ACE2) as a receptor and depends on TMPRSS2 protease activity. Here, we searched the genomes of metazoans from different classes using an extensive BLASTP survey and found ACE2 and TMPRSS2 occur in vertebrates, but some vertebrates lack Tmprss2. We identified 6 amino acids among 25 known human ACE2 residues are highly associated with the binding of ACE2 to SARS-CoV-2 (p value < .01) by Fisher exact test, and following this, calculated the probability of viral attachment within each species by the randomForest function from R randomForest library. Furthermore, we observed that Ace2 selected from seven animals based on the above analysis lack the hydrophobic contacts identified on human ACE2, indicating less affinity of SARS-CoV-2 to Ace2 in animals than humans. Finally, the alignment of 3D structure between human ACE2 and other animals by I-TASSER and TM-align displayed a reasonable structure for viral attachment within these species. Taken together, our data may shed light on the human-to-animal transmission of SARS-CoV-2.

D020022:Genetic Predisposition to Disease


The Correlation between Mathematics Anxiety, Numerical Ability and Drug Calculation Ability of Paramedic Students: An Explanatory Mixed Method Study.

Abstract:
Introduction
Numeracy is the ability to reason and to apply simple numerical concepts. Numerical and drug calculation skills are essential for patient safety. Health-care providers who perform drug calculation in their work required good math skills, especially numerical ability. The aims of this study were to explore the relationship between numerical ability, math anxiety and drug calculation performance and to explore the factors that contribute to drug calculation ability among paramedic students.

Methods
A sequential explanatory mixed-method approach that included a paper-based questionnaire followed by face-to-face interviews was used in this study. The participants completed a 30-minute survey that is composed of demographics, the 10-item Mathematics Anxiety Rating Scale (MARS), a 12-question numerical ability test (NAT) and a 9-question drug calculation ability test (DCAT) and then were invited for a structured interview.

Results
The mean MARS scores were higher for the second-year students than the third students. The NAT and DCAT scores for the third-year students were higher than the second-year students. There was a significant difference in the mean drug calculation ability test scores (DCAT) (t (106) = 2.13, p = 0.035 and Cohen's d = 0.43 between males (5.05 (2.32)) and females (4.03 (2.43))). Math education prior joining the university (beta = 0.862, p = 0.030) made the strongest unique contribution when controlling for the other variables followed by numerical ability (beta =0.25, p <0.001). The themes that emerged from the interviews included the impact of technology, classmates' impact, mathematics competence and the mental block.

Conclusion
Drug calculation is fundamental in paramedic practice. It is affected by the numerical ability of the students and is negatively and indirectly impacted by mathematics anxiety. Modifications of a paramedic program curriculum can improve student's ability to think critically and to overcome medication dosage problems.

anxiety
paramedics
allied health personnel
drug dosage calculation
gender


Towards personalized antithrombotic management with drugs and devices across the cardiovascular spectrum.

Abstract: Intravascular thrombus formation and embolization are among the most frequent events leading to a number of cardiovascular conditions with high morbidity and mortality. The underlying causes are stasis of the circulating blood, genetic and acquired coagulation disorders, and reduced antithrombotic or prothrombotic properties of the vascular wall (Virchow's triad). In the venous system, intravascular thrombi can cause venous thrombosis and pulmonary and even peripheral embolism including ischaemic stroke [through a patent foramen ovale (PFO)]. Thrombi in the left atrium and its appendage or ventricle form in the context of atrial fibrillation and infarction, respectively. Furthermore, thrombi can form on native or prosthetic aortic valves, within the aorta (in particular at sites of ulcers, aortic dissection, and abdominal aneurysms), and in cerebral and peripheral arteries causing stroke and critical limb ischaemia, respectively. Finally, thrombotic occlusion may occur in arteries supplying vital organs such the heart, brain, kidney, and extremities. Thrombus formation and embolization can be managed with anticoagulants and devices depending on where they form and embolize and on patient characteristics. Vitamin K antagonists are preferred in patients with mechanical valves, while novel oral anticoagulants are first choice in most other cardiovascular conditions, in particular venous thromboembolism and atrial fibrillation. As anticoagulants are associated with a risk of bleeding, devices such as occluders of a PFO or the left atrial appendage are preferred in patients with an increased bleeding risk. Platelet inhibitors such as aspirin and/or P2Y12 antagonists are preferred in the secondary prevention of coronary artery disease, stroke, and peripheral artery disease either alone or in combination depending on the clinical condition. A differential and personalized use of anticoagulants, platelet inhibitors, and devices is recommended and reviewed in this article.

Atrial fibrillation
Platelets
Coronary artery disease
Peripheral arterial disease
Coagualtion
Dual antiplatelet therapy
Left atrial occlusion
NOAC
Pulmonary embolism


Non-Washed Resorbable Blasting Media (NWRBM) on Titanium Surfaces could Enhance Osteogenic Properties of MSCs through Increase of miRNA-196a And VCAM1.

Abstract: Surface topography of Titanium (Ti) dental implants strongly influences osseointegration. In the present work, we have analyzed the influence of two Ti implant surfaces characterized by similar microtopography but different nanotopography and chemistry on the osteoblastic phenotype of Dental Pulp Stem Cells (DPSCs). The effect on osteogenic differentiation, extracellular matrix (ECM) and cell adhesion molecules production have been evaluated by means of molecular biology analyses. The morphology of the cells grown onto these surfaces has been analyzed with SEM and immunofluorescence (IF), and the safety of the surfaces has been tested by using karyotype analysis, Ames test and hemocompatibility assay. Results showed that starting from 15 days of DPSCs culture, a substantial expression of osteoblast specific markers and a strong increase of cell adhesion molecules can be detected. In particular, when DPSCs are seeded on the Ti implants expression of microRNA (miRNA)-196a, which is involved in osteoblastic commitment of stem cells, and of Vascular Cell Adhesion Molecule 1 (VCAM1), a factor involved in angiogenesis, is strongly enhanced.

Gardin|Chiara|C| Ferroni|Letizia|L| Piattelli|Adriano|A| SIvolella|Stefano|S| Zavan|Barbara|B| Mijiritsky|Eitan|E|

D019010:Vascular Cell Adhesion Molecule-1

Titanium
surfaces
Dental implant
osseointegration
Nanotopography
Stem cells
Titanium implants


Positive Outcomes of Optimizing Student-Preceptor Continuity in a Traditional Block Clerkship.

Abstract:
PROBLEM
Student-preceptor discontinuity during 3rd-year clerkships limits the quality and quantity of supervision, teaching, and feedback. Although longitudinal integrative clerkships increase continuity and are associated with improved student and preceptor experience, they require schoolwide curricular reform. Alternative innovations enhancing student-preceptor relationships within the constraints of a traditional block clerkship may demonstrate similar benefits.

INTERVENTION
We piloted a continuity-enhanced general pediatric ambulatory schedule during 2 consecutive clerkship blocks in 2013. Students in the continuity-enhanced model (n = 29) were assigned 1-3 primary clinic preceptors, whereas those in the traditional model (n = 30) worked with 5-8. Data were gathered from student assessments and anonymous student and preceptor surveys. We used t and Fisher's exact tests to compare the two groups and performed thematic analysis of free-text survey comments.

CONTEXT
Our school utilizes a block clerkship model with approximately 30 students rotating through the pediatric clerkship every 8 weeks. During the 3-week ambulatory portion, students spend 8 half days in the general pediatric ambulatory clinic. At the conclusion of each clinic, attendings completed brief student evaluation cards. Traditionally, student and attending schedules were created independently, resulting in transient supervisory relationships and dissatisfaction with clinical engagement, feedback, and evaluation.

OUTCOME
Seventy-three percent (43/59) of the students completed the survey. Ten general ambulatory attendings collectively completed 87.5% (35/40) of the monthly surveys. Continuity students received significantly more narrative evaluation comments (10.6 vs. 5.8, p <. 001) from general ambulatory clinic attendings and were more likely to have at least one general ambulatory clinic attending endorse being able to provide meaningful feedback and evaluation (n = 29, 100% vs. n = 20, 66.7%, p <. 001). Continuity students were also more likely to endorse being able to ask at least one of these attendings for a letter of recommendation (71.4% vs. 9.1%, p <. 001) and to have at least one general ambulatory clinic attending endorse being able to provide a meaningful letter of recommendation if asked (62.1% vs. 3.3%, p <. 001). Students (88.4%) and attendings (85.7%) preferred the continuity-enhanced schedule. The most frequent theme of both student and attending free-text survey remarks were relationships and assessment.

LESSONS LEARNED
Intentional scheduling of clerkship students to enhance preceptor continuity resulted in significant positive outcomes echoing the relationship-based educational benefits of longitudinal clerkships, particularly in regards to student assessment and feedback. Clerkship directors and other medical educators should consider implementing small changes within block clerkships to maximize student-preceptor continuity.

feedback
clinical clerkship
medical faculty
preceptorship
undergraduate medical education


MicroRNA-24 Modulates Staphylococcus aureus-Induced Macrophage Polarization by Suppressing CHI3L1.

Abstract: Macrophages play a crucial role in host innate anti-Staphylococcus aureus defense, which is tightly regulated by multiple factors, including microRNAs. A recent study showed that miR-24 plays an important role in macrophage polarization. Here, we investigated the biological function of miR-24 in S. aureus-stimulated macrophages. The results revealed that miR-24 expression was significantly decreased in both human and mouse macrophage cell lines with S. aureus stimulation in a time-dependent manner. Moreover, miR-24 overexpression significantly decreased the production of M1 phenotype markers, such as IL-6, iNOS, TNF-α, CD86, and CD80, whereas it increased the production of M2 markers, such as Arg1, CCL17, CCL22, CD163, and CD206, in S. aureus-stimulated macrophages. Conversely, knockdown of miR-24 promoted M1 macrophage polarization but diminished M2 macrophage polarization in S. aureus-stimulated macrophages. Furthermore, CHI3L1 was predicted as a target gene of miR-24 using bioinformatics software and identified by luciferase reporter assay. Additionally, miR-24 overexpression inhibited CHI3L1 expression and downregulated the downstream MAPK pathway in S. aureus-stimulated macrophages. Finally, CHI3L1 overexpression rescued macrophage polarization and MAPK pathway inhibition induced by miR-24 mimic transfection in S. aureus-stimulated macrophages. In conclusion, the data suggest that miR-24 serves as a molecular regulator in S. aureus-induced macrophage polarization through targeting of CHI3L1 and regulation of the MAPK pathway, which may provide a promising therapeutic target for S. aureus-related infections and inflammatory diseases.

Jingjing|Zhang|Z| Nan|Zhang|Z| Wei|Wu|W| Qinghe|Guo|G| Weijuan|Wang|W| Peng|Wang|W| Xiangpeng|Wang|W|

D020929:Mitogen-Activated Protein Kinase Kinases


Extracorporeal circulatory approaches to treat acute respiratory distress syndrome.

Abstract: The early history of extracorporeal membrane oxygenation (ECMO) for adult patients with the acute respiratory distress syndrome (ARDS) evolved slowly over decades, a consequence of extracorporeal technology with high risk and unclear benefit. However, advances in component technology, accumulating evidence, and growing experience in recent years have resulted in a resurgence of interest in ECMO. Extracorporeal support, though currently lacking high-level evidence, has the potential to improve outcomes, including survival, in ARDS. In the near future, novel extracorporeal management strategies may, in fact, lead to a new paradigm in the approach to certain patients with ARDS.

Acute respiratory distress syndrome
Extracorporeal membrane oxygenation
Extracorporeal carbon dioxide removal
Lung-protective ventilation
Respiratory failure


Shoot tip culture: a step towards 13C metabolite flux analysis of sink leaf metabolism.

Abstract:
Background
Better understanding of the physiological and metabolic status of plants can only be obtained when metabolic fluxes are accurately assessed in a growing plant. Steady state 13C-MFA has been established as a routine method for analysis of fluxes in plant primary metabolism. However, the experimental system needs to be improved for continuous carbon enrichment from labelled sugars into metabolites for longer periods until complex secondary metabolism reaches steady state.

Results
We developed an in vitro plant culture strategy by using peppermint as a model plant with minimizing unlabelled carbon fixation where growing shoot tip was strongly dependent on labelled glucose for their carbon necessity. We optimized the light condition and detected the satisfactory phenotypical growth under the lower light intensity. Total volatile terpenes were also highest at the same light. Analysis of label incorporation into pulegone monoterpene after continuous U-13C6 glucose feeding revealed nearly 100% 13C, even at 15 days after first leaf visibility (DALV). Label enrichment was gradually scrambled with increasing light intensity and leaf age. This study was validated by showing similar levels of label enrichment in proteinogenic amino acids. The efficiency of this method was also verified in oregano.

Conclusions
Our shoot tip culture depicted a method in achieving long term, stable and a high percentage of label accumulation in secondary metabolites within a fully functional growing plant system. It recommends the potential application for the investigations of various facets of plant metabolism by steady state 13C-MFA. The system also provides a greater potential to study sink leaf metabolism. Overall, we propose a system to accurately describe complex metabolic phenotypes in a growing plant.

Secondary metabolism
Mentha piperita
Metabolic flux analysis
Shoot culture
Sink leaves


Acute Myeloid Leukemia With Recurrent Cytogenetic Abnormalities.

Abstract:
OBJECTIVES
Session 1 of the 2013 Society for Hematopathology/European Association for Hematopathology Workshop was devoted to the cases of acute myeloid leukemia (AML) with recurrent cytogenetic abnormalities.

METHODS
Based on World Health Organization 2008 criteria, seven specific translocations are defined as "recurrent" in AML. Of these seven, three are considered to be AML defining regardless of blast percentage. Workshop cases provided the opportunity to consider potential new AML-defining cytogenetic mutations, as well as other unique aspects of AML with cytogenetic abnormalities.

RESULTS
Most of the 38 cases submitted were acute promyelocytic leukemia (APL) with t(15;17)(q24.1;q21.1) and so-called variants (12 cases), AML with t(8;21)(q22;q22) (seven cases), AML with inv(3)(q11q26.2) (six cases), and AML with 11q23 translocations (five cases).

CONCLUSIONS
This review focuses on providing updated recommendations for the rapid diagnosis of APL, discussing the types and significance of variant RARA mutations in APL-like leukemias, and refining low-blast-count (oligoblastic) AML. In addition, the significance of unique morphologic, immunophenotypic, and genetic variations in AML defined by a recurrent cytogenetic abnormality is included.

D006801:Humans
D015470:Leukemia, Myeloid, Acute
D014178:Translocation, Genetic

Cytogenetics
AML
Recurrent abnormalities


The effect of an enriched environment on activity levels in people with stroke in an acute stroke unit: protocol for a before-after pilot study.

Abstract:
BACKGROUND
Clinical practice guidelines advocate engaging stroke survivors in as much activity as possible early after stroke. One approach found to increase activity levels during inpatient rehabilitation incorporated an enriched environment (EE), whereby physical, cognitive, and social activity was enhanced. The effect of an EE in an acute stroke unit (ASU) has yet not been explored.

METHODS/DESIGN
We will perform a prospective non-randomized before-after intervention study. The primary aim is to determine if an EE can increase physical, social, and cognitive activity levels of people with stroke in an ASU compared to usual care. Secondary aims are to determine if fewer secondary complications and improved functional outcomes occur within an EE. We will recruit 30 people with stroke to the usual care block and subsequently 30 to the EE block. Participants will be recruited within 24-72 h after onset of stroke, and each block is estimated to last for 12 weeks. In the usual care block current management and rehabilitation within an ASU will occur. In the EE block, the ASU environment will be adapted to promote greater physical, social, and cognitive activity. Three months after the EE block, another 30 participants will be recruited to determine sustainability of this intervention. The primary outcome is change in activity levels measured using behavioral mapping over 12 h (7.30 am to 7.30 pm) across two weekdays and one weekend day within the first 10 days of admission. Secondary outcomes include functional outcome measures, adverse and serious adverse events, stroke survivor, and clinical staff experience.

DISCUSSION
There is a need for effective interventions that starts directly in the ASU. The EE is an innovative intervention that could increase activity levels in stroke survivors across all domains and promote early recovery of stroke survivors in the acute setting.

TRIAL REGISTRATION
Australian New Zealand Clinical Trial Registry, ANZCTN12614000679684.

Rosbergen|Ingrid C M|IC|
Grimley|Rohan S|RS|
Hayward|Kathryn S|KS|
Walker|Katrina C|KC|
Rowley|Donna|D|
Campbell|Alana M|AM|
McGufficke|Suzanne|S|
Robertson|Samantha T|ST|
Trinder|Janelle|J|
Janssen|Heidi|H|
Brauer|Sandra G|SG|

Enriched environment
Activity
Stroke
Acute stroke unit
Complications
Behavioral mapping


Relationships between the integrity and function of lumbar nerve roots as assessed by diffusion tensor imaging and neurophysiology.

Abstract:
PURPOSE
Diffusion tensor imaging (DTI) has shown promise in the measurement of peripheral nerve integrity, although the optimal way to apply the technique for the study of lumbar spinal nerves is unclear. The aims of this study are to use an improved DTI acquisition to investigate lumbar nerve root integrity and correlate this with functional measures using neurophysiology.

METHODS
Twenty healthy volunteers underwent 3 T DTI of the L5/S1 area. Regions of interest were applied to L5 and S1 nerve roots, and DTI metrics (fractional anisotropy, mean, axial and radial diffusivity) were derived. Neurophysiological measures were obtained from muscles innervated by L5/S1 nerves; these included the slope of motor-evoked potential input-output curves, F-wave latency, maximal motor response, and central and peripheral motor conduction times.

RESULTS
DTI metrics were similar between the left and right sides and between vertebral levels. Conversely, significant differences in DTI measures were seen along the course of the nerves. Regression analyses revealed that DTI metrics of the L5 nerve correlated with neurophysiological measures from the muscle innervated by it.

CONCLUSION
The current findings suggest that DTI has the potential to be used for assessing lumbar spinal nerve integrity and that parameters derived from DTI provide quantitative information which reflects their function.

Chiou|S Y|SY|
Hellyer|P J|PJ|
Sharp|D J|DJ|
Newbould|R D|RD|
Patel|M C|MC|
Strutton|P H|PH|

Diffusion tensor imaging
Neurophysiology
Nerve integrity
Electrical stimulation
Spinal nerve roots
Transcranial magnetic stimulation


Immune checkpoint inhibition in COVID-19: risks and benefits.

Abstract:
INTRODUCTION
Immune checkpoint inhibition (ICI) is a novel cancer immunotherapy, which is administered in patients with metastatic, refractory, or relapsed solid cancer types. Since the initiation of the Coronavirus Disease 2019 (COVID-19) pandemic, many studies have reported a higher severity and mortality rate of COVID-19 among patients with cancer in general.

AREAS COVERED
The immunomodulatory effects of ICI can modify the patients' immune system function in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is controversy over whether the severity of COVID-19 in cancer patients who previously received ICI compared to other patients with cancer has increased. There is evidence that the upregulation of immune checkpoint molecules in T cells, lymphopenia, and inflammatory cytokine secretion are associated with the severity of COVID-19 symptoms.

EXPERT OPINION
ICI can interrupt the T cell exhaustion and depletion by interrupting the inhibitory signaling of checkpoint molecules in T cells, and augments the immune system response in COVID-19 patients with lymphopenia. However, ICI may also increase the risk of cytokine release syndrome. ICI can be considered not only as a cancer immunotherapy but also as immunotherapy in COVID-19. More studies are needed to assess the safety of ICI in COVID-19 patients with or without cancer.


Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein-Protein Interaction.

Abstract: The structure-based design of M-525 as the first-in-class, highly potent, irreversible small-molecule inhibitor of the menin-MLL interaction is presented. M-525 targets cellular menin protein at sub-nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL-regulated gene expression in MLL leukemia cells. M-525 demonstrates high cellular specificity over non-MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co-crystal structure of M-525 in complex with menin firmly establish its mode of action. A single administration of M-525 effectively suppresses MLL-regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M-525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia.

Xu|Shilin|S| Aguilar|Angelo|A| Xu|Tianfeng|T| Zheng|Ke|K| Huang|Liyue|L| Stuckey|Jeanne|J| Chinnaswamy|Krishnapriya|K| Bernard|Denzil|D| Fernández-Salas|Ester|E| Liu|Liu|L| Wang|Mi|M| McEachern|Donna|D| Przybranowski|Sally|S| Foster|Caroline|C| Wang|Shaomeng|S|0000-0002-8782-6950

D054730:Protein Interaction Domains and Motifs

irreversible inhibitors
menin-MLL protein-protein interaction
MLL leukemia
drug design


An overview of microRNAs: Biology, functions, therapeutics, and analysis methods.

Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.

microRNA
therapeutics
gene expression
epigenetics
intercellular communication


Views and Experiences of Travelers from US States to Zika-Affected Areas.

Abstract: Travelers to areas with Zika virus transmission are at risk of infection and of transmitting the virus after returning home. While protective behaviors during and after travel can reduce these risks, information about traveler practices or underlying views is limited. We examined these issues using data from the first representative poll of travelers from US states to Zika-affected areas, including US territories and Miami, Florida, conducted December 1 to 23, 2016. We analyzed results among all travelers (n = 1,285) and 2 subgroups at risk for pregnancy-related complications: (1) travelers in households where someone was pregnant or considering pregnancy (n = 72), and (2) other travelers of reproductive age (n = 631). We also examined results among those with different levels of awareness and knowledge about Zika virus. Results show that in households where someone was pregnant or considering pregnancy, awareness of Zika in the destination, concern about infection, and adoption of protective behaviors was relatively high. That said, sizable shares of travelers as a whole did not know information about asymptomatic and sexual transmission or post-travel behaviors. Further, concern about getting infected during travel was low among travelers as a whole, including other travelers of reproductive age. Few travelers consistently adopted protective behaviors during or after travel. Even among travelers who were aware of Zika in their destination and knew how to protect themselves, adoption of protective behaviors was only slightly higher. Findings from this poll suggest communications may be more effective if tailored to different levels of true and perceived risk. To address gaps in knowledge about transmission and post-travel protective behaviors, messaging should include facts and acknowledge the complexities of novel information and social context. Consideration should also be given to emphasizing other benefits of Zika protective behaviors or prioritizing behaviors that are most feasible.

SteelFisher|Gillian K|GK|
Caporello|Hannah|H|
Blendon|Robert J|RJ|
Ben-Porath|Eran N|EN|
Lubell|Keri|K|
Friedman|Allison L|AL|
Holton|Kelly|K|
Smith|Belinda J|BJ|
McGowan|Ericka|E|
Schafer|Thomas|T|

D007722:Health Knowledge, Attitudes, Practice

Travel
Zika
Infectious diseases
Risk communication


Utility of fluorodeoxyglucose positron emission tomography/computed tomography for early diagnosis and evaluation of disease activity of relapsing polychondritis: a case series and literature review.

Abstract:
OBJECTIVE
Relapsing polychondritis (RPC) is relatively rare and early diagnosis is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for the diagnosis of RPC and evaluation of disease activity.

METHODS
Five RPC patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from a total of 13 patients were analysed.

RESULTS
Typical FDG accumulation was noted in the tracheobronchial trees of nine patients, the costal cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses of three, auricles of three, lymph nodes of three and the aorta of one. One patient showed nasal chondritis on a PET scan despite the absence of nasal changes on physical examination. Of five patients with costochondritis, four remained asymptomatic. Of nine patients with airway FDG accumulation, eight developed respiratory symptoms and all had CT abnormalities. In the other patient, airway FDG accumulation was evident despite the absence of airway symptoms and a lack of abnormalities in the respiratory function test and CT. PET also revealed bronchial chondritis in asymptomatic patients. The mean maximum standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d. 2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement.

CONCLUSION
FDG-PET/CT is a potentially powerful tool for the early diagnosis of RPC, especially in patients without easily biopsied organ involvement. This modality also facilitates evaluation of disease extent and disease activity during treatment.

Yamashita|Hiroyuki|H| Takahashi|Hiroyuki|H| Kubota|Kazuo|K| Ueda|Yo|Y| Ozaki|Takashi|T| Yorifuji|Hideki|H| Bannai|Ei|E| Minamimoto|Ryogo|R| Morooka|Miyako|M| Miyata|Yoko|Y| Okasaki|Momoko|M| Takahashi|Yuko|Y| Kaneko|Hiroshi|H| Kano|Toshikazu|T| Mimori|Akio|A|

cartilage
respiratory
diagnostic imaging
ears
nose
radionuclide imaging
throat


Esophageal Squamous Cell Carcinoma After Adjustable Gastric Banding.

Abstract: The prevalence of morbid obesity has been increasing worldwide. Therefore, multiple laparoscopic adjustable gastric bandings (LAGBs) have been placed in Belgium in the nineties. The procedure was considered as minimal invasive with low morbidity rates. However, some publication cases suggest a possible association between LAGB and the onset of an esophageal cancer. We present a case of a 49-year-old female who consulted for dysphagia, epigastric pain, and anorexia 17 years after LAGB. An esophageal squamous cell carcinoma was diagnosed in the distal esophagus, close to the lap band. The diagnostic value of the performed contrast swallow study seemed limited. We suggest that a routinely gastroscopic evaluation in the long-term follow-up after LAGB should be strived for in patients presenting with late-onset dysphagia.

D000077277:Esophageal Squamous Cell Carcinoma

Esophageal
Squamous cell carcinoma
Gastric banding


Suicide Rates in Nordic Prisons 2000-2016.

Abstract:
OBJECTIVE
To compare suicide rates of people in prison and the general population in the Nordic countries.

METHODS
Data on deaths by suicide and person-years for people in prison and the general population were obtained for the Nordic countries during 2000-2016. Age-standardized rate ratios were calculated.

RESULTS
The suicide rate in the Nordic countries overall was 110.1 (95% CI = 98.1, 122.2) per 100,000 person-years for people in prison. A significant decline was noted for the suicide rate of people in prison between 2000 and 2016 (p < 0.0001). The age-standardized mortality ratio was 7.4 (95% CI = 5.9-8.2) for males and 17.8 (95% CI = 7.3-33.2) for females in Denmark, Iceland, and Norway.

CONCLUSION
Despite a decreasing trend over time, excess suicide mortality was noted for people in prison.

Morthorst|Britt Reuter|BR|
Mehlum|Lars|L|
Pàlsson|Sigurdur P|SP|
Mühlmann|Charlotte|C|
Hammerlin|Yngve|Y|
Madsen|Trine|T|
Nordentoft|Merete|M|
Erlangsen|Annette|A|0000-0003-3475-0558

D012537:Scandinavian and Nordic Countries

suicide
prison
Nordic countries
Age-standardized rate ratio
imprisonment


Brown adipose tissue: Updates in cellular and molecular biology.

Abstract: Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP) -1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM) -16. The sympathetic nervous system centrally regulates thermogenesis through norepinephrine, which acts on the adrenergic receptors of BAT. This bound leads to the initialization of the many pathways that may activate thermogenesis in acute and/or chronic ways. In summary, this mini-review aims to demonstrate the latest advances in the knowledge of BAT.

Bargut|Thereza Cristina Lonzetti|TC|
Aguila|Marcia Barbosa|MB|
Mandarim-de-Lacerda|Carlos Alberto|CA|

D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Brown adipose tissue
Brown adipocytes
Non-shivering thermogenesis
Obesity
Uncoupling protein 1


Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial.

Abstract:
LESSONS LEARNED
Administration of autologous invariant natural killer T (iNKT) cells was safe and well-tolerated in patients with hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage B/C). Expanded iNKT cells produced T-helper 1-like responses with possible antitumor activity. No severe adverse events were observed in any of the enrolled patients, including one patient who received 1010 in vitro-expanded autologous iNKT cells as a single infusion.

BACKGROUND
Invariant natural killer T cells co-express T-cell antigen receptor and natural killer (NK) cell receptors. Invariant natural killer T (iNKT) cells exhibit antitumor activity, but their numbers and functions are impaired in patients with hepatocellular carcinoma (HCC). The adoptive transfer of iNKT cells might treat advanced HCC.

METHODS
This phase I study (NCT03175679) enrolled 10 patients with HCC (Barcelona Clinic Liver Cancer [BCLC] stage B/C) at Beijing YouAn Hospital (April 2017 to May 2018). iNKT cells isolated from peripheral blood mononuclear cells (PBMCs) were expanded and alpha-galactosylceramide (α-GalCer)-pulsed. Dosage escalated from 3 × 107 to 6 × 107 to 9 × 107 cells/m2 (3+3 design). An exploratory dose trial (1 × 1010 cells/m2 ) was conducted in one patient.

RESULTS
Expanded iNKT cells produced greater quantities of T-helper 1 (Th1) cytokines (e.g., interferon-gamma, perforin, and granzyme B) but less interleukin-4 than nonexpanded iNKT cells. Circulating numbers of iNKT cells and activated NK cells were increased after iNKT cell infusion. Most treatment-related adverse events were grade 1-2, and three grade 3 adverse events were reported; all resolved without treatment. Four patients were progression-free at 5.5, 6, 7, and 11 months after therapy, and one patient was alive and without tumor recurrence at the last follow-up. Five patients died at 1.5 to 11 months after treatment.

CONCLUSION
Autologous iNKT cell treatment is safe and well-tolerated. Expanded iNKT cells produce Th1-like responses with possible antitumor activity. The antitumor effects of iNKT cell infusion in patients with advanced HCC merit further investigation.

Natural killer T cells
Immunotherapy
Hepatocellular carcinoma


Classification of patients with non-alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers.

Abstract:
AIM
Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression.

METHODS
We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay.

RESULTS
Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2-binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated.

CONCLUSION
Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely.

Mizuno|Masayuki|M| Shima|Toshihide|T| Oya|Hirohisa|H| Mitsumoto|Yasuhide|Y| Mizuno|Chiemi|C| Isoda|Satoshi|S| Kuramoto|Mizue|M| Taniguchi|Masanori|M| Noda|Masashi|M| Sakai|Kyoko|K| Koyama|Noriyuki|N| Okanoue|Takeshi|T|

non-alcoholic fatty liver disease
type IV collagen
fibrosis
non-alcoholic steatohepatitis


Shock index predicts up to 90-day mortality risk after intracerebral haemorrhage.

Abstract:
BACKGROUND
Shock index (SI - heart rate/systolic blood pressure) has been studied as a measure of haemodynamic status. We aimed to determine whether SI measures within 72 h of admission were associated with adverse outcomes in intracerebral haemorrhage (ICH).

METHODS
Patients were drawn from the Virtual International Stroke Trials Archive-Intracerebral Haemorrhage (VISTA-ICH). Multivariable Cox regressions modelled the relationship between SI (on admission, 24, 48, 72 h) and mortality (at 3-, 7-, and 90-days), 90-day incident pneumonia and cardiovascular events (MACE). Ordinal logistic regressions modelled the relationship between SI and 90-day modified Rankin Scale (mRS).

RESULTS
979 patients were included. Baseline SI was not associated with mortality. 24 h SI > 0.7 was associated with 7-day mortality (hazard ratio (95% confidence interval) = 3.14 (1.37-7.19)). 48 h and 72 h SI > 0.7 were associated with 7-day (4.23 (2.07-8.66) and 3.24 (1.41-7.42) respectively) and 90-day mortality (2.97 (1.82-4.85) and 2.05 (1.26-3.61) respectively). SI < 0.5 at baseline, 48 h and 72 h was associated with decreased pneumonia risk. 24 h and 48 h SI > 0.7was associated with increased MACE risk. 48 h and 72 h SI > 0.7 was associated with increased odds of higher 90-day mRS.

CONCLUSION
Higher-than-normal SI subsequent to initial encounter was associated with higher post-ICH mortality at 3, 7, and 90 days. Lower-than-normal SI was associated with a decreased risk of incident pneumonia.

Pana|Tiberiu A|TA|
Quinn|Terence J|TJ|
Perdomo-Lampignano|Jesus A|JA|
Szlachetka|Weronika A|WA|
Knoery|Charles|C|
Mamas|Mamas A|MA|
Myint|Phyo K|PK|
|||

Shock index
Mortality
Intracerebral haemorrhage
Blood pressure
Stroke


Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson's disease.

Abstract:
BACKGROUND
Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide.

OBJECTIVE
Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication.

METHODS
All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson's disease, were invited for a further follow up assessment at the UCL Institute of Neurology. This visit included all 20 individuals who had previously completed twelve months exposure to exenatide 10ug bd and the 24 individuals who had acted as randomised controls. Motor severity of PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the MDS-UPDRS, together with several non-motor tests. This assessment was thus 24 months after their original baseline visit, i.e. 12 months after cessation of exenatide.

RESULTS
Compared to the control group of patients, patients previously exposed to exenatide had an advantage of 5.6 points (95% CI, 2.2-9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3 points; (95% CI, 9.3-1.4; p = 0.006) between the 2 groups on the Mattis Dementia Rating scale.

CONCLUSIONS
While these data must still not be interpreted as evidence of neuroprotection, they nevertheless provide strong encouragement for the further study of this drug as a potential disease modifying agent in Parkinson's disease.

Aviles-Olmos|Iciar|I| Dickson|John|J| Kefalopoulou|Zinovia|Z| Djamshidian|Atbin|A| Kahan|Joshua|J| Ell|Peter|P| Whitton|Peter|P| Wyse|Richard|R| Isaacs|Tom|T| Lees|Andrew|A| Limousin|Patricia|P| Foltynie|Thomas|T|

exenatide
Parkinson's disease
UPDRS
clinical trial
diabetes mellitus
disease modifying treatment


METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function.

Abstract: Methyltransferase-like protein 16 (METTL16) is a human RNA methyltransferase that installs m6A marks on U6 small nuclear RNA (U6 snRNA) and S-adenosylmethionine (SAM) synthetase pre-mRNA. METTL16 also controls a significant portion of m6A epitranscriptome by regulating SAM homeostasis. Multiple molecular structures of the N-terminal methyltransferase domain of METTL16, including apo forms and complexes with S-adenosylhomocysteine (SAH) or RNA, provided the structural basis of METTL16 interaction with the coenzyme and substrates, as well as indicated autoinhibitory mechanism of the enzyme activity regulation. Very recent structural and functional studies of vertebrate-conserved regions (VCRs) indicated their crucial role in the interaction with U6 snRNA. METTL16 remains an object of intense studies, as it has been associated with numerous RNA classes, including mRNA, non-coding RNA, long non-coding RNA (lncRNA), and rRNA. Moreover, the interaction between METTL16 and oncogenic lncRNA MALAT1 indicates the existence of METTL16 features specifically recognizing RNA triple helices. Overall, the number of known human m6A methyltransferases has grown from one to five during the last five years. METTL16, CAPAM, and two rRNA methyltransferases, METTL5/TRMT112 and ZCCHC4, have joined the well-known METTL3/METTL14. This work summarizes current knowledge about METTL16 in the landscape of human m6A RNA methyltransferases.

METTL16
U6 snRNA
SAM homeostasis
m6A methyltransferases


A New Approach to Predicting Cryptocurrency Returns Based on the Gold Prices with Support Vector Machines during the COVID-19 Pandemic Using Sensor-Related Data.

Abstract: In a real-world situation produced under COVID-19 scenarios, predicting cryptocurrency returns accurately can be challenging. Such a prediction may be helpful to the daily economic and financial market. Unlike forecasting the cryptocurrency returns, we propose a new approach to predict whether the return classification would be in the first, second, third quartile, or any quantile of the gold price the next day. In this paper, we employ the support vector machine (SVM) algorithm for exploring the predictability of financial returns for the six major digital currencies selected from the list of top ten cryptocurrencies based on data collected through sensors. These currencies are Binance Coin, Bitcoin, Cardano, Dogecoin, Ethereum, and Ripple. Our study considers the pre-COVID-19 and ongoing COVID-19 periods. An algorithm that allows updated data analysis, based on the use of a sensor in the database, is also proposed. The results show strong evidence that the SVM is a robust technique for devising profitable trading strategies and can provide accurate results before and during the current pandemic. Our findings may be helpful for different stakeholders in understanding the cryptocurrency dynamics and in making better investment decisions, especially under adverse conditions and during times of uncertain environments such as in the COVID-19 pandemic.

gold
digital currency
SARS-CoV-2
artificial intelligence
data science
machine learning
sensing and data extraction


Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue.

Abstract: Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy.

Veljković|Andrej|A|0000-0001-5950-7517 Hadži-Dokić|Jovan|J| Sokolović|Dušan|D|0000-0001-6586-6428 Bašić|Dragoslav|D| Veličković-Janković|Ljubinka|L| Stojanović|Marko|M| Popović|Dejan|D| Kocić|Gordana|G|

xanthine oxidase
oxidative stress
prostate cancer


Utilization of CRISPR Interference To Validate MmpL3 as a Drug Target in Mycobacterium tuberculosis.

Abstract: There is an urgent need for novel therapeutics to treat Mycobacterium tuberculosis infections. Genetic strategies for validating novel targets are available, yet their time-consuming nature limits their utility. Here, using MmpL3 as a model target, we report on the application of mycobacterial CRISPR interference for the rapid validation of target essentiality and compound mode of action. This strategy has the potential to rapidly accelerate tuberculosis drug discovery.

D064112:Clustered Regularly Interspaced Short Palindromic Repeats


The complete mitochondrial genome of the bazaar fly, Musca sorbens Wiedemann (Diptera: Muscidae).

Abstract: The bazaar fly, Musca sorbens (Diptera: Muscidae) Wiedemann, 1830 is a world-wide species with sanitary, medical, and veterinary importance. The complete mitochondrial genome of M. sorbens is sequenced to better understand the mitogenomic characteristics and phylogeny of this species. The circular mitogenome is 16,120 bp in length, contains 13 protein-coding genes (PCGs), 22 tRNA genes (tRNAs), two rRNA genes, and an AT-rich control region. The mitogenome comprises an A + T content of 77.4%. All PCGs start with "ATN" codons except for COI which starts with TCG, and terminate with the common stop codons TNN. A phylogenetic tree, including six Muscidae species, is reconstructed based on the whole mitogenome sequences. The interspecific distances of mitogenomes between the six Muscidae species range from 0.059 to 0.168.

mitochondrial genome
bazaar fly
Musca sorbens
Muscidae
phylogenetic analysis


Raman Molecular Fingerprints of SARS-CoV-2 British Variant and the Concept of Raman Barcode.

Abstract: The multiple mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have created variants with structural differences in both their spike and nucleocapsid proteins. While the functional relevance of these mutations is under continuous scrutiny, current findings have documented their detrimental impact in terms of affinity with host receptors, antibody resistance, and diagnostic sensitivity. Raman spectra collected on two British variant sub-types found in Japan (QK002 and QHN001) are compared with that of the original Japanese isolate (JPN/TY/WK-521), and found bold vibrational differences. These included: i) fractions of sulfur-containing amino acid rotamers, ii) hydrophobic interactions of tyrosine phenol ring, iii) apparent fractions of RNA purines and pyrimidines, and iv) protein secondary structures. Building upon molecular scale results and their statistical validations, the authors propose to represent virus variants with a barcode specially tailored on Raman spectrum. Raman spectroscopy enables fast identification of virus variants, while the Raman barcode facilitates electronic recordkeeping and translates molecular characteristics into information rapidly accessible by users.

Raman fingerprints SARS-CoV-2 variants barcode


Complete mitochondrial genome of Glomeridesmus spelaeus (Diplopoda, Glomeridesmida), a troglobitic species from iron-ore caves in Eastern Amazon.

Abstract: We report the complete mitochondrial genome sequence of Glomeridesmus spelaeus, the first sequenced genome of the order Gomeridesmida. The genome is 14,825 pb in length and encodes 37 mitochondrial (13 PCGs, 2 rRNA genes, 22 tRNA) genes and contains a typical AT-rich region. The base composition of the mitogenome was A (40.1%), T (36.4%), C (15.8%), and G (7.6%), with an GC content of 23.5%. Our results indicated that G. spelaeus is only distantly related to the other Diplopoda species with available mitochondrial genomes in the public databases. As the broadest genetic characterization of a Glomeridesmida species available to date, the mitogenome of G. spelaeus will help understanding the evolution of such a little-known millipede group. Also, our data will be important for the characterization and conservation of the diverse invertebrate troglofauna of the Amazonian caves.

troglobite
mitogenome
Millipede
Serra dos Carajás


Differences in Adherence to Common Inhaled Medications in COPD.

Abstract:
OBJECTIVE
To study differences in adherence to common inhaled medications in COPD.

METHODS
Adherence of 795 patients was recorded from pharmacy records over 3 years in the COMIC cohort. It was expressed as percentage and deemed good at ≥75-≤125%, sub-optimal ≥50-<75%, and poor <50% (underuse) or >125% (overuse). Most patients used more than one medication, so we present 1379 medication periods.

RESULTS
The percentages of patients with good therapy adherence ranged from 43.2 (beclomethasone) -75.8% (tiotropium); suboptimal from 2.3 (budesonide) -23.3% (fluticasone); underuse from 4.4 (formoterol/budesonide) -18.2% (beclomethasone); and overuse from 5.1 (salmeterol) -38.6% (budesonide). Patients using fluticasone or salmeterol/fluticasone have a 2.3 and 2.0-fold increased risk of suboptimal versus good adherence compared to tiotropium. Patients using salmeterol/fluticasone or beclomethasone have a 2.3- and 4.6-fold increased risk of underuse versus good adherence compared to tiotropium. Patients using budesonide, salmeterol/fluticasone, formoterol/budesonide, ciclesonide and beclomethasone have an increased risk of overuse versus good adherence compared to tiotropium. Adherence to inhalation medication is inversely related to lung function.

CONCLUSION
Therapy adherence to inhalation medication for the treatment of COPD is in our study related to the medication prescribed. Tiotropium showed the highest percentage of patients with good adherence, followed by ciclesonide, both dosed once daily. The idea of improving adherence by using combined preparations cannot be confirmed in this study. Further research is needed to investigate the possibilities of improving adherence by changing inhalation medication.

Koehorst-ter Huurne|Kirsten|K|
Movig|Kris|K|
van der Valk|Paul|P|
van der Palen|Job|J|
Brusse-Keizer|Marjolein|M|

D058666:Adrenergic beta-2 Receptor Agonists

D029424:Pulmonary Disease, Chronic Obstructive

adherence
inhalation medication
COPD
lung function


NaOH-HCl neutralized urine preparation for direct testing of uropathogens by Bruker MS.

Abstract:
BACKGROUND
We evaluated the analytical performance of a NaOH-HCl neutralization protocol for identifying uropathogens directly from urine samples by a Bruker MS system (Bruker Daltonics, German) and sought to establish a protocol for integrating the method with conventional screening.

METHODS
Among all urine samples requested for Gram staining, UF-1000i, and urine cultures by physicians, we selected samples that were positive by both Gram staining and UF-1000i testing. Urine was prepared by neutralization using 0.01M NaOH-HCl, and the samples were processed by Bruker MS. For the low detection limit, one strain each of Escherichia coli and Enterococcus faecium was inoculated in sterile deionized water and sterile urine specimens at sequential dilutions.

RESULTS
In a total of 1270 urine samples, 125 samples (9.8%) were positive by both Gram staining and UF-1000i. Of 94 samples showing a single morphotype on agar plates, 82 samples had colony counts ≥105  CFU/mL and most uropathogens (95.1%, 78 of 82) had UF-1000i counts ≥106  bacteria/mL. Among them, Bruker MS correctly identified 86.6% (71/82) of all isolates, 89.2% (66/74) of Gram-negative bacteria (GNB), and 62.5% (5/8) of Gram-positive cocci (GPC) with higher average scores for GPC (mean score 2.013) and GNB (mean score 2.110).

CONCLUSIONS
Bruker MS with urine preparation by NaOH-HCl neutralization provides a simple, cost-effective, and accurate method for identifying uropathogens directly from urine. Using Bruker MS when single morphotype Gram staining and the UF-1000i count as ≥106  bacteria/mL may improve the efficiency of bacterial identification in routine practice.

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

NaOH-HCl neutralization
Bruker MS
direct identification
urine screening tests


Safety and efficacy of a feed additive consisting on the bacteriophages PCM F/00069, PCM F/00070, PCM F/00071 and PCM F/00097 infecting Salmonella Gallinarum B/00111 (Bafasal®) for all avian species (Proteon Pharmaceuticals S.A.).

Abstract: Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the feed additive consisting of four bacteriophages infecting Salmonella Gallinarum B/00111 (PCM F/00069, PCM F/00070, PCM F/00071 and PCM F/00097, trade name: Bafasal®) when used as a zootechnical additive in water for drinking and liquid complementary feed for all avian species. The effects sought are the reduction of the Salmonella spp. carriage in chickens for fattening, the improvement of their performance, or both. The host strain harbours an acquired antimicrobial resistance gene. No viable cells or DNA from the host organism were found in the additive. The four phages proved to be strictly lytic and to have a machinery allowing to package a unit-length of the viral genome. The manufacturing process excludes the presence of remnants from the propagation process in the final additive. Consequently, no concerns are expected from the nature and manufacture of the product. Considering this and the results of the tolerance study with chickens for fattening, the Panel concluded that Bafasal® is safe for all avian species. Considering the nature and manufacturing process of the additive, Bafasal® is not expected to pose a risk for consumers. The results of the subchronic oral toxicity study and genotoxicity studies provided support this conclusion. Exposure of users via inhalation is expected to be low, but Bafasal® should be considered a respiratory sensitiser. No conclusions were drawn on the irritancy of Bafasal® to skin and eyes or on its dermal sensitisation potential due to lack of data. Considering the nature and manufacturing process of the additive, Bafasal® is safe for the environment. The Panel was not in the position to conclude on the efficacy of Bafasal® for any avian species due to insufficient data.

|||
Bampidis|Vasileios|V|
Azimonti|Giovanna|G|
Bastos|Maria de Lourdes|ML|
Christensen|Henrik|H|
Dusemund|Birgit|B|
Kouba|Maryline|M|
Durjava|Mojca Fašmon|MF|
López-Alonso|Marta|M|
López Puente|Secundino|S|
Marcon|Francesca|F|
Mayo|Baltasar|B|
Pechová|Alena|A|
Petkova|Mariana|M|
Ramos|Fernando|F|
Sanz|Yolanda|Y|
Villa|Roberto Edoardo|RE|
Woutersen|Ruud|R|
Cocconcelli|Pier Sandro|PS|
Glandorf|Boet|B|
Herman|Lieve|L|
Prieto Maradona|Miguel|M|
Saarela|Maria|M|
Dierick|Noël|N|
Martelli|Giovanna|G|
Brantom|Paul|P|
Tosti|Luca|L|
Svensson|Kettil|K|
Anguita|Montserrat|M|
Galobart|Jaume|J|
Innocenti|Matteo|M|
Pettenati|Elisa|E|
Revez|Joana|J|
Brozzi|Rosella|R|

Salmonella enterica ser. Gallinarum B/00111


Patterns of social participation among older adults with disabilities and the relationship with well-being: A latent class analysis.

Abstract:
AIM
Living with a chronic condition or a disability at older age impacts social participation. Social connections and social activities seem interrelated leading to heterogeneous patterns in social participation. The aim of this study was to identify a typology in social participation among older adults with disabilities, and to relate this typology to their background characteristics and well-being measures.

METHODS
A total of 1775 older adults with disabilities or chronic conditions aged 65-97 were sampled from a nationwide panel study in the Netherlands. Social participation was assessed by various measures related to social connections, social informal activities, voluntary work, effort to increase social participation, and online social participation. A latent class analysis was carried out to identify a typology of social participation. Differences between these classes were explored with multinomial regression analyses and pairwise comparisons.

RESULTS
Four classes were found: social withdrawers (22.5%, n = 399), proximate social dwellers (14.5%, n = 257), moderately active social dwellers (37.2%, n = 660) and pro-active social dwellers (25.9%, n = 459). Background characteristics, such as living alone and severity of disability, differed significantly among classes. Regarding well-being measures, it appeared that pro-active social dwellers had the most positive scores. Social withdrawers were most prone to reduced life satisfaction and health related quality of life and increased loneliness and experienced participation restrictions.

CONCLUSIONS
A typology with four patterns based on a wide spectrum of social participation aspects in older adults with disabilities was identified. This typology may help to assess the risk for reduced well-being of older adults with disabilities.

van Hees|Suzanne G M|SGM|
van den Borne|Bart H P|BHP|
Menting|Juliane|J|
Sattoe|Jane N T|JNT|

Social participation
Disability
Latent class analysis
Chronic condition
Older age
Elderly


Incidence of Multiple Sclerosis in Germany: A Cohort Study Applying Different Case Definitions Based on Claims Data.

Abstract:
BACKGROUND
Data on the incidence of multiple sclerosis (MS) on the national level is scarce. We aimed to estimate the incidence of MS in Germany and to compare different MS case definitions based on claims data.

METHODS
We conducted a cohort study with the German Pharmacoepidemiological Research Database in 2012 and calculated age- and gender-standardized incidence rates (sIRs) for 3 case definitions. In addition, the effect of stepwise reduction of the look-back period without MS diagnosis on the incidence rate was evaluated.

RESULTS
Our cohort comprised 4,175,877 individuals. The first case definition based on ICD-10 diagnoses yielded an sIR of 21.8 (95% CI 20.2-23.5) per 100,000 person years, whereas the second and third case definitions with additional requirements for drug treatment and diagnostic tests resulted in lower sIRs of 10.1 (9.1-11.3) and 6.6 (5.8-7.6) respectively. We observed a higher incidence for shorter look-back periods.

CONCLUSION
The incidence of MS in Germany might be substantially higher than suggested in earlier studies. In addition, our study highlights the importance of a look-back period of at least 36 months to identify incident MS cases based on claims data.

Schmedt|Niklas|N| Khil|Laura|L| Berger|Klaus|K| Riedel|Oliver|O|

D038801:International Classification of Diseases

Incidence
Multiple sclerosis
Germany
Cohort study
Case definitions
Databases
Epidemiology
Immunosuppressive agents


Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis.

Abstract: Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue (glands and stroma) outside the uterus, mainly in the peritoneal cavity, ovaries, and intestines. This condition shows estrogen dependency and progesterone resistance, and it has been associated with chronic inflammation, severe pain, and infertility, which negatively affect the quality of life in reproductive women. The molecular mechanisms involved in the pathogenesis of endometriosis are not completely understood; however, inflammation plays a key role in the pathophysiology of the disease, mainly by altering the function of immune cells (macrophages, natural killer, and T cells) and increasing levels of pro-inflammatory mediators in the peritoneal cavity, endometrium, and blood. These immune alterations inhibit apoptotic pathways and promote adhesion and proliferation of endometriotic cells, as well as angiogenesis and neurogenesis in endometriotic lesions. It has been demonstrated that hormonal alterations in endometriosis are related to the inflammatory unbalance in this disease. Particularly, steroid hormones (mainly estradiol) promote the expression and release of pro-inflammatory factors. Excessive inflammation in endometriosis contributes to changes of hormonal regulation by modulating sex steroid receptors expression and increasing aromatase activity. In addition, dysregulation of the inflammasome pathway, mediated by an alteration of cellular responses to steroid hormones, participates in disease progression through preventing cell death, promoting adhesion, invasion, and cell proliferation. Furthermore, inflammation is involved in endometriosis-associated infertility, which alters endometrium receptivity by impairing biochemical responses and decidualization. The purpose of this review is to present current research about the role of inflammasome in the pathogenesis of endometriosis as well as the molecular role of sex hormones in the inflammatory responses in endometriosis.

García-Gómez|Elizabeth|E|
Vázquez-Martínez|Edgar Ricardo|ER|
Reyes-Mayoral|Christian|C|
Cruz-Orozco|Oliver Paul|OP|
Camacho-Arroyo|Ignacio|I|
Cerbón|Marco|M|

inflammation
inflammasome
sex steroid hormones
endometriosis
pro-inflammatory factors
bacteria
estrogen receptor
progesterone receptor


Short versus long cephalomedullary nailing of intertrochanteric fractures: a meta-analysis of 3208 patients.

Abstract:
OBJECTIVES
The purpose of the study was to compare treatment outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures.

DATA SOURCES
A systematic review of perioperative outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures was performed. The following databases were used: using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-2019), and MEDLINE (1980-2019). The queries were performed in June 2019.

STUDY SELECTION
The following search term query was used: "Intramedullary Nail AND Intertrochanteric Fracture OR "Long OR Short Nail AND intertrochanteric Fracture." Studies were excluded if they were "single-arm" studies (i.e., reporting on either long or short CMN but not both), or did not report at least one of the outcomes being meta-analyzed. Furthermore, cadaveric studies, animal studies, basic science articles, editorial articles, surveys and studies were excluded.

DATA EXTRACTION
Two investigators independently reviewed abstracts from all identified articles. Full-text articles were obtained for review if necessary, to allow further assessment of inclusion and exclusion criteria. Additionally, all references from the included studies were reviewed and reconciled to verify that no relevant articles were missing from the systematic review.

DATA SYNTHESIS
Short nails were associated with statistically significantly less estimated blood loss and operative time compared to long nails. There were no significant differences in transfusion rates, implant failures or overall re-operation rates between implant lengths. Similarly, there was no significant difference in peri-implant fracture between implant lengths.

CONCLUSIONS
Overall, the available clinical evidence supports the use of short cephalomedullary nails for the majority of intertrochanteric femur fractures.

STUDY DESIGN/LEVEL OF EVIDENCE
Meta-analysis; Level III, therapeutic.

Cinque|Mark E|ME|
Goodnough|L Henry|LH|
Md|Blake J Schultz|BJS|
Fithian|Andrew T|AT|
DeBaun|Malcolm|M|
Lucas|Justin F|JF|
Md|Michael J Gardner|MJG|
Bishop|Julius A|JA|

Cephalomedullary nail
Intertrochanteric femur fracture
Short nail
Long nail


Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication.

Abstract: Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.

Kang|Qian|Q|0000-0001-5825-1660 Xu|Jinghang|J| Luo|Hao|H| Tan|Ning|N|0000-0001-9917-2192 Chen|Hongyu|H| Cheng|Ran|R|0000-0001-6975-3498 Pan|Jiali|J|0000-0002-3448-7430 Han|Yifan|Y| Yang|Yuqing|Y| Liu|Dan|D| Xi|Hongli|H| Yu|Min|M| Xu|Xiaoyuan|X|

D000998:Antiviral Agents
D001219:Aspartate Aminotransferases
D015415:Biomarkers
D016174:Hepacivirus
D006526:Hepatitis C
D019698:Hepatitis C, Chronic
D006801:Humans
D008103:Liver Cirrhosis
D011446:Prospective Studies

Aspartate aminotransferase/platelet ratio index (APRI)


The Presence of the DNA Repair Genes mutM, mutY, mutL, and mutS is Related to Proteome Size in Bacterial Genomes.

Abstract: DNA repair is expected to be a modulator of underlying mutation rates, however the major factors affecting the distribution of DNA repair pathways have not been determined. The Proteomic Constraint theory proposes that mutation rates are inversely proportional to the amount of heredity information contained in a genome, which is effectively the proteome. Thus, organisms with larger proteomes are expected to possess more efficient DNA repair. We show that an important factor influencing the presence or absence of four DNA repair genes mutM, mutY, mutL, and mutS is indeed the size of the bacterial proteome. This is true both of intracellular and other bacteria. In addition, the relationship of DNA repair to genome GC content was examined. In principle, if a DNA repair pathway is biased in the types of mutations it corrects, this may alter the genome GC content. The presence of the mismatch repair genes mutL and mutS was not correlated with genome GC content, consistent with their involvement in an unbiased DNA repair pathway. In contrast, the presence of the base excision repair genes mutM and mutY, whose products both correct GC → AT mutations, was positively correlated with genome GC content, consistent with their biased repair mechanism. Phylogenetic analysis however indicates that the relationship between the presence of mutM and mutY genes and genome GC content is not a simple one.

Garcia-Gonzalez|Aurian|A|
Rivera-Rivera|Ruben J|RJ|
Massey|Steven E|SE|

DNA repair
proteome size
bacterial genome
AT bias


Effect of air flow rate and C/N ratio on biological nitrogen removal through the CANON process treating reject water.

Abstract: The CANON process is a promising method for nitrogen removal in wastewaters with low organic carbon content like reject water. This study investigated the effect of important factors for optimization of the CANON process through inhibition of nitrite-oxidizing bacteria (NOB). In the acclimation period, complete ammonium removal and 43.3% total N removal were obtained at hydraulic retention time of 12 h, temperature of 30°C ± 0.5°C and DO equal to 7-9 mg/L. The effects of air flow rate (AFR) (representative of DO), SRT and C/N were evaluated. Air flow rate was the most important factor for controlling the process, but the effect of SRT was negligible. When AFR was increased from 100 to 500 mL/min, both ammonium removal efficiency (33-43% to 81-83%) and nitrite accumulation (nitritation, 40 mgN/L to 100-120 mgN/L) were increased, but with increasing AFR to 1000 mL/min only ammonium removal efficiency was increased and because of better condition (high DO) for NOBs, nitritation was decreased. C/N had an effect like AFR of 1000 and only increased ammonium removal efficiency and total N removal. With increasing AFR and C/N, both OUR and AUR were increased, but SVI was decreased.

Mousavi|Seyyed Alireza|SA|
Mehralian|Mohammad|M|
Khashij|Maryam|M|
Ibrahim|Shaliza|S|

air flow rate
CANON process
reject water
OUR
AUR
BNR


Dual-mobility cups could yield lesser infections than conventional cups: a meta-analysis of comparative studies.

Abstract:
INTRODUCTION
Dual-mobility cups (DMC) are gaining popularity mainly for their reduced rate of dislocation following total hip arthroplasty (THA). Currently, indication for DMC use extends beyond patients with high risk of dislocation or revision THA cases. Many authors reported DMC outcomes in primary THA for all aetiologies. However, some reports claimed that the use of DMC is accompanied with higher rates of infection compared with conventional cups (CC) in both primary and revision THA.

RESEARCH QUESTION
Does the use of DMC generate higher rates of infection when compared with conventional cups?

OBJECTIVES
The aim of this meta-analysis was to look for significant difference in the rate of post-operative infection between DMC cups and conventional cups.

METHODOLOGY
MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar were searched since inception. Only studies with comparative design reporting the outcome infection rate were included.

RESULTS
Seventeen retrospective comparative studies were located comprising 248,541 patients: 16,020 in the DMC group and 232,521 in the CC group. The mean follow-up period was 37.5 ± 42 and 50.2 ± 48.7 months for the DMC and CC groups, respectively. The meta-analytical results indicated the following: (a) significantly lesser infections following DMC compared with CC in revision THA (odds ratio (OR) = 0.75 (95% CI = 0.653 to 0.874, P = 0.0002, I2 = 25%); (b) for primary THA and for large-sampled registries, significance was found using only the fixed-effects model estimate; and (c) no significant difference was found for the subgroup of cohort studies.

CONCLUSION
Our results clearly refute the claim that DMC would yield higher rates of infection. On the contrary, the findings demonstrated that the use of DMC reduces the risk of post-operative infection in revision THA and a similar lower infection trend for primary THA when compared with the standard cups.

Assi|Chahine|C|
Mansour|Jad|J|
Prudhon|Jean Louis|JL|
Caton|Jacques|J|
Yammine|Kaissar|K|0000-0003-0094-9892

D019644:Arthroplasty, Replacement, Hip
D006617:Hip Dislocation
D006622:Hip Prosthesis
D006801:Humans
D011474:Prosthesis Design
D011475:Prosthesis Failure
D012086:Reoperation
D012189:Retrospective Studies

Dual-mobility cups
Conventional cups
Post-operative infection
Standard cups
Primary total hip arthroplasty
Revision total hip arthroplasty