Temporal and spatial regulation of eukaryotic DNA replication: from regulated initiation to genome-scale timing program.

Abstract: Replication origins are where pre-replication complexes are assembled during G1 phase. However, only a subset of the origins is actually "fired" to initiate DNA synthesis during S phase. Whereas factors involved in these steps are relatively well understood now, the mechanisms behind the origin specification, the choice of origins to be fired and determination of their timing are still under active investigation. Recent data show that the origin positions as well as the selection of those to be fired may be determined by multiple factors including sequences, chromatin context, epigenetic information, and some specific genomic features, but that the choice is surprisingly plastic and opportunistic. Timing regulation of firing, on the other hand, appears to be related to cell type-specific intrinsic chromatin architecture in nuclei. The conserved Rif1 protein appears to be a major global regulator of the genome-wide replication timing. Replication timing is regulated also by other factors including checkpoint signals, local chromatin structures, timing and quantity of pre-RC formation, and availability of limiting initiation factors.

Renard-Guillet|Claire|C| Kanoh|Yutaka|Y| Shirahige|Katsuhiko|K| Masai|Hisao|H|

Replication origins
Pre-replicative complex
Rif1
Replication timing
Chromatin loop


Is pull-through an acceptable replacement for low anterior resection for rectal cancers in low-income setting? A case-control study.

Abstract:
Background
Colorectal cancers are the second most common cancers overall and are the third deadliest cancers. Complete resection is the treatment of choice for rectal cancers and chemoradiotherapy (CRT) is strongly recommended in stage 2 and 3. Low anterior resection (LAR) is the most common procedure used, but it requires the use of stapler which might be very expensive as one study estimated the median cost of LAR inpatients to be over 13.000 USD. However, coloanal pull-through (PT) used to be the common procedure before introducing staplers in the twentieth century and can be less expensive, but with higher complication rates.

Materials and methods
This is a retrospective case-control study from patients' records who underwent either LAR or PT for their rectal cancer in Syria. All patients had either stage 2 or 3 cancer and were treated by the same group of surgeons and received the same adjuvant and neoadjuvant CRT protocol. Patients from both groups had the same prognosis and stages.

Results
This study included 60 participants, of which, 30 had LAR and 30 had PT. They all had successful removal of the cancer and follow-ups were for 1 year after the surgery. There were no significant differences between the two procedures in post-operative leak, urinary retention, stricture, sexual function and recurrence (p > 0.05). However, post-operative incontinence was more frequent with PT (p = 0.027).

Conclusion
PT can be an acceptable substitute of LAR in low income settings despite having higher incidence of incontinence.

Ghareeb|Amjad|A|
Kakaje|Ameer|A|
Ghareeb|Ayham|A|
Alahmar|Fadi Obaid|FO|

SPSS, Statistical Package for the Social Sciences

STROCSS, Strengthening the reporting of cohort studies in surgery


Simple optical method for measuring free shrinkage.

Abstract:
OBJECTIVES
A simple optical method for measuring polymerization shrinkage of dental composites is compared with an established dilatometer.

METHODS
Five restorative composites were used to test the methods: Filtek Supreme Ultra (3M ESPE), Filtek LS (3M ESPE), Premise (Kerr), Gradia Direct (GC), and GC Kalore (GC). Uncured composites were attached to sandblasted silane-treated glass slides. The slides were placed sample side inside a mercury-filled dilatometer (ADAF). The mercury levels were recorded as the materials were light-cured through the glass-slides (40s). Mercury levels, which correlated with volumetric shrinkage, were recorded for 60min (N=6). For the optical method, uncured composite was placed on a smooth silicone platform. A pre-polymerization image was captured under a stereomicroscope, and the specimen was light-cured (40s). Post-polymerization images were captured at 2, 10, 60, and 90min (N=10). Composite outlines were traced to obtain projected surface areas (ImageJ) and volumetric shrinkage was calculated. Results were analyzed using two-way ANOVA (α=0.05) and Pearson Correlation tests. Shrinkage deformation for both methods was modeled using finite element analysis.

RESULTS
Volumetric shrinkage at 60min ranged between 1.24% and 2.24% for dilatometer and 1.35-2.68% for optical methods. Optical method shrinkage was consistently higher than the dilatometer (P=.0001), but the ranking of the composites was the same (Pearson Correlation Coefficient 0.9997). Finite element analysis showed that lower shrinkage values of the dilatometer method could be attributed to bonding of its samples.

SIGNIFICANCE
The optical method using a general-purpose stereomicroscope and public-domain software is a simple and accurate alternative to measure free shrinkage.

Tantbirojn|Daranee|D|
Pfeifer|Carmem S|CS|
Amini|Arianna N|AN|
Versluis|Antheunis|A|

D003188:Composite Resins
D003799:Dental Stress Analysis
D008422:Materials Testing
D058105:Polymerization

Free shrinkage
Polymerization shrinkage
Dilatometer
Stereomicroscope
Finite element analysis
Image analysis software
Resin composite


Report and Abstracts of the 17th Meeting of IIM, the Interuniversity Institute of Myology:Virtual meeting, October 16-18, 2020.

Abstract: In 2020, due to the COVID-19 pandemic, the annual meeting of the Interuniversity Institute of Myology (IIM), took place on a virtual platform. Attendees were scientists and clinicians, as well as pharmaceutical companies and patient organization representatives from Italy, several European countries, Canada and USA. Four internationally renowned Keynote speakers presented recent advances on muscle stem cells regulation, skeletal muscle regeneration, quantitative biology approaches, and metabolic regulation of muscle homeostasis. Novel, unpublished data by young trainees were presented as oral communications or posters, in five scientific sessions and two poster sessions. On October 15, 2020, selected young trainees participated to the High Training Course on "Advanced Myology", organized together with the University of Perugia, Italy. The course, on a virtual platform, showcased lectures on muscle development and regulation of muscle gene expression by international speakers, and roundtables discussions on "Single cell analysis of skeletal muscle" and "Skeletal muscle stem cell in healthy muscle and disease". The Young IIM Committee, composed by young trainee winners of awards in the past IIM Meeting editions, was directly involved in the selection of keynote speakers, the organization of scientific sessions and roundtables discussions tailored to the interests of their peers. A broad audience of Italian, European and North American participants contributed to the different initiatives. The meeting was characterized by a friendly and inclusive atmosphere, facilitating lively and stimulating discussions on emerging areas of muscle research. The meeting stimulated scientific cross-fertilization fostering novel ideas and scientific collaborations aimed at better understanding muscle normal physiology and the mechanisms underlaying muscle diseases, with the ultimate goal of developing better therapeutic strategies. The meeting was a success, and the number of meeting attendees was the highest of all IIM Meeting editions. Despite the current difficulties imposed by the COVID-19 pandemic, we are confident that the IIM community will continue to grow and deliver significant contributions to the understanding of muscle development and function, the pathogenesis of muscular diseases and the development of novel therapeutic approaches. Here, abstracts of the meeting illustrate the new results on basic, translational, and clinical research, confirming that our field is strong and healthy.

stem cells
regeneration
metabolism
homeostasis
muscle development
translational
cachexia
clinical trials
dystrophy
epigenetics
ex-vivo
in-vivo
neuromuscular
proof of concept
sarcopenia
wasting


The uptake and effectiveness of online cognitive behaviour therapy for symptoms of anxiety and depression during COVID-19.

Abstract:
BACKGROUND
The mental health impacts of COVID-19 have been considerable with many individuals experiencing significant anxiety and depression. Online cognitive behavioural therapy (iCBT) programs provide scalable access to psychological interventions, however the effectiveness of these programs during the pandemic has not been investigated. This study examined the uptake and effectiveness of iCBT for symptoms of anxiety and depression during the first eight months of the pandemic in Australia (March- October 2020) and compared outcomes to the 12 months prior to COVID-19.

METHODS
6,132 adults commenced iCBT (5,074 during the pandemic and 1,058 in the year before) and completed measures of anxiety and depression symptom severity, and psychological distress pre- and post-treatment.

RESULTS
In the COVID-19 period, we observed a 504% increase in the number of monthly course registrations compared to the year prior (with a peak increase of 1,138% between April and June 2020). Baseline anxiety and depression symptom severity were similar for the COVID and pre-COVID groups. Prior to and during the pandemic, the iCBT course was associated with large effect size reductions in anxiety (g = 0.94-1.18) and depression (g = 0.92-1.12) symptom severity, as well as psychological distress (g = 1.08-1.35).

LIMITATIONS
lack of control group and long-term follow-up, as well as lack of detailed information about course users (e.g., health status and life context).

CONCLUSION
Results indicate the considerable increase in demand for psychological support during the COVID-19 pandemic in Australia and demonstrate the effectiveness and scalability of iCBT for symptoms of anxiety and depression.

Mahoney|Alison|A|
Li|Ian|I|
Haskelberg|Hila|H|
Millard|Michael|M|
Newby|Jill M|JM|

Effectiveness
Anxiety
Depression
iCBT
Pandemic
Internet intervention
Self-help


Solid cancer risk dependence on the Pasquill-Gifford atmospheric stability classes in a radiological event.

Abstract: In a radiological event, the lack of preliminary information about the site of explosion and the difficulty in predicting the accurate path and distribution of radioactive plumes makes it difficult to predict expected health effects of exposed individuals. So far, in such a health evaluation, radiation-induced stochastic health effects such as cancer are not included. The Pasquill-Gifford atmospheric classes generally allow connecting atmospheric stability with dispersion of radioactive contaminants to the environment. In this work, an environmental release of radioactive Cs-137 was simulated and the resulting relative risk for solid cancer incidence among the affected population calculated. The HotSpot health physics code was used to simulate the radioactive atmospheric dispersion and calculate the Total Effective Dose Equivalent (TEDE), which was then used to estimate the relative risk of cancer incidence. The main results from this work suggest that the relative cancer risk and atmospheric stability classes are linked by differences in the TEDE. Such a finding may support triage, because it adds additional information on the potentially affected population at the early stages of an emergency response.

Bulhosa|Valquiria M|VM|
Funcke|Renata P N|RPN|
Brum|Tercio|T|
Sanchez|Juliana S|JS|
Lima|Zelmo R|ZR|
Vital|Hélio C|HC|
Prah|Matjaž|M|
Andrade|Edson R|ER|0000-0001-8800-6105

Solid cancer
Relative risk
Environmental radiation
Gaussian simulation


Transcriptomic and Proteomic Analysis of Drought Stress Response in Opium Poppy Plants during the First Week of Germination.

Abstract: Water deficiency is one of the most significant abiotic stresses that negatively affects growth and reduces crop yields worldwide. Most research is focused on model plants and/or crops which are most agriculturally important. In this research, drought stress was applied to two drought stress contrasting varieties of Papaver somniferum (the opium poppy), a non-model plant species, during the first week of its germination, which differ in responses to drought stress. After sowing, the poppy seedlings were immediately subjected to drought stress for 7 days. We conducted a large-scale transcriptomic and proteomic analysis for drought stress response. At first, we found that the transcriptomic and proteomic profiles significantly differ. However, the most significant findings are the identification of key genes and proteins with significantly different expressions relating to drought stress, e.g., the heat-shock protein family, dehydration responsive element-binding transcription factors, ubiquitin E3 ligase, and others. In addition, metabolic pathway analysis showed that these genes and proteins were part of several biosynthetic pathways most significantly related to photosynthetic processes, and oxidative stress responses. A future study will focus on a detailed analysis of key genes and the development of selection markers for the determination of drought-resistant varieties and the breeding of new resistant lineages.

transcriptomics
proteomics
opium poppy
Papaver somniferum
dehydrins
drought response
gene expression
plant stress


Adjustment of therapeutic LMWH to achieve specific target anti-FXa activity does not affect outcomes in pregnant patients with venous thromboembolism.

Abstract: Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality in the developed world. Low molecular weight heparins (LMWH) are routinely used to provide therapeutic anticoagulation during pregnancy for women with VTE, with measurement of plasma anti-FXa activity used to guide dosing in certain patient groups. There is limited evidence to support the use of anti-FXa monitoring in pregnant patients. This study seeks to ascertain whether anti-FXa monitoring of pregnant patients with VTE influences patient outcomes. We performed a single-centre case series including two consecutive groups of pregnant patients treated with LMWH for VTE sustained in the index pregnancy with and without monitoring of anti-FXa levels. 35,394 patients delivered during the study period in a large urban stand-alone maternity hospital, with 26 cases of VTE eligible for inclusion. There was no significant difference between the two groups in any clinical outcome; including maternal blood loss at delivery, recurrent thromboembolic events or rates of planned delivery. These data provide clinical evidence to support current international guideline recommendations that measurement of plasma anti-FXa activity in the majority of patients receiving therapeutic-intensity antenatal LMWH is not warranted.

McDonnell|Brendan P|BP|
Glennon|Kate|K|
McTiernan|Aoife|A|
O'Connor|Hugh D|HD|
Kirkham|Colin|C|
Kevane|Barry|B|
Donnelly|Jennifer C|JC|
Ni Áinle|Fionnuala|F|

Low molecular weight heparin
Pregnancy
Factor Xa
Tinzaparin
Venous thrombosis


Comparison of two models of surface display of xylose reductase in the Saccharomyces cerevisiae cell wall.

Abstract: In order to display xylose reductase at the surface of S. cerevisiae cells two different gene constructs have been prepared. In the first, xylose reductase gene GRE3 was fused with two parts of the CCW12 gene, the N-terminal one coding for the secretion signal sequence, and the C-terminal coding for the glycosylphosphatidylinositol anchoring signal. Transformed cells synthesized xylose reductase and incorporated it in the cell wall through the remnant of the glycosylphosphatidylinositol anchor. The other construct was prepared by fusing the GRE3 with the PIR4 gene coding for one of the proteins of the Pir-family containing the characteristic N-terminal repetitive sequence that anchors Pir proteins to β-1,3-glucan. In this way xylose reductase was covalently attached to glucan through its N-terminus. For the expression of the constructs either the GAL1, or the PHO5 promoters have been used. Both strains displayed active xylose reductases and their enzyme properties were compared with the control enzyme bearing the secretion signal sequence but no anchoring signals, thus secreted into the medium. The enzyme displayed through the N-terminal fusion with PIR4 had higher affinity for xylose than the other construct, but they both expressed somewhat lower affinity than the control enzyme. Similarly, the Km values for NADPH of both immobilized enzymes were somewhat higher than the Km of the control XR. Both displayed enzymes, especially the one fused with Pir4, had higher thermal and pH stability than the control, while other enzymatic properties were not significantly impaired by surface immobilization.

Hossain|Amir Sk|AS|
Teparić|Renata|R|
Mrša|Vladimir|V|

Surface display
Xylose reductase
Cell wall protein
Genetic immobilization
Yeast cell wall


A roadmap for evaluating the use and value of durable ventricular assist device therapy.

Abstract: Heart failure is a disease characterized by profound human suffering with limitations in survival despite treatment with guideline-directed medical therapies. Patients with heart failure frequently progress to advanced stages and often require cardiac transplantation or implantation of left ventricular assist devices (LVADs) to extend survival and improve quality of life. As the number of suitable heart donors, number of experienced medical centers and patient comorbidities place restrictions on the feasibility of cardiac transplantation, implantation of LVADs has emerged as a more frequently applied treatment as either a bridge to transplantation or as permanent therapy. Considerable data have documented improvements in survival, functional status and quality of life offered by LVADs, however, few studies have focused on identifying: (1) determinants of LVAD use across medical centers, (2) the relationship between the determinants of LVAD use and value (defined as quality divided by cost), and (3) how determinants of LVAD use are influenced or impacted by vulnerable populations. We propose a conceptual model that integrates the main determinants of LVAD utilization, which include technology, insurance coverage, market-, provider- and patient-level factors. We propose this paradigm as a necessary prerequisite for understanding LVAD usage and value. This conceptual framework provides a broader view for future studies, which are needed to inform emerging healthcare policies that influence dissemination of this expensive but life-prolonging medical therapy.

Ward|Sarah T|ST|
Liang|Qixing|Q|
Pagani|Francis D|FD|
Zhang|Min|M|
Kormos|Robert L|RL|
Aaronson|Keith D|KD|
Althouse|Andrew D|AD|
Nallamothu|Brahmajee K|BK|
Likosky|Donald S|DS|

D000078337:Procedures and Techniques Utilization

heart failure
left ventricular assist device
bridge to transplant
factors
durable LVAD therapy


Single-stage revision of MRSA orthopedic device-related infection in sheep with an antibiotic-loaded hydrogel.

Abstract: Local antimicrobial therapy is an integral aspect of treating orthopedic device-related infection (ODRI), which is conventionally administered via polymethyl-methacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

single-stage revision
MRSA
hydrogel
local antibiotics
fracture-related infection
orthopaedic device-related infection
peri-prosthetic joint infection


IR microspectroscopic identification of microplastics in municipal wastewater treatment plants.

Abstract: Municipal wastewater treatment plants (WWTPs) have been identified as a key source of microplastics (MPs) release into rivers and oceans. Varied extents of MPs pollution have been observed at different WWTPs with limited information in Thailand. This research aimed to study the occurrence of MPs in municipal WWTPs in Thailand by measuring MPs of three WWTPs which employ different treatment process. The WWTPs were selected to represent MP pollution from urbanized and suburbanized areas with different treatment set-ups, i.e., sequence batch reactor (WWTP-A), oxidation ditch (WWTP-B), and conventional activated sludge (WWTP-C). Water and sludge sampling was performed at the inlet and outlet of primary and secondary treatment units. The results indicate that the average MPs removal efficiency of the WWTPs was ca. 84%, with the aeration tank as the main removal unit by transferring MPs from the water phase to sludge. Primary treatment comprising of screening and grit chambers could not remove MPs effectively. Most of the MPs observed in the WWTPs were fibers (32-57%), mostly made of polyester, polyethylene, polyacrylate, and polypropylene. From these results, it is suggested to implement tertiary treatment options to improve MPs removal efficiency in WWTPs, and to apply post-treatment to the WWTPs' raw sludge to prevent the MPs' release into the environment when the sludge is applied to agricultural land.

Hongprasith|Narapong|N| Kittimethawong|Chakrit|C| Lertluksanaporn|Rawit|R| Eamchotchawalit|Theepop|T| Kittipongvises|Suthirat|S| Lohwacharin|Jenyuk|J|

Microplastics
Municipal wastewater treatment
Aeration
FTIR spectroscopy
Fate of microplastics


Roles of the Pumilio domain protein PUF3 in Trypanosoma brucei growth and differentiation.

Abstract: Trypanosomes strongly rely on post-transcriptional mechanisms to control gene expression. Several Opisthokont Pumilio domain proteins are known to suppress expression when bound to mRNAs. The Trypanosoma brucei Pumilio domain protein PUF3 is a cytosolic mRNA-binding protein that suppresses expression when tethered to a reporter mRNA. RNA-binding studies showed that PUF3 preferentially binds to mRNAs with a classical Pumilio-domain recognition motif, UGUA[U/C]AUU. RNA-interference-mediated reduction of PUF3 in bloodstream forms caused a minor growth defect, but the transcriptome was not affected. Depletion of PUF3 also slightly delayed differentiation to the procyclic form. However, both PUF3 genes could be deleted in cultured bloodstream- and procyclic-form trypanosomes. Procyclic forms without PUF3 also grew somewhat slower than wild-type, but ectopic expression of C-terminally tagged PUF3 impaired their viability. PUF3 was not required for RBP10-induced differentiation of procyclic forms to bloodstream forms. Mass spectrometry revealed no PUF3 binding partners that might explain its suppressive activity. We conclude that PUF3 may have a role in fine-tuning gene expression. Since PUF3 is conserved in all Kinetoplastids, including those that do not infect vertebrates, we suggest that it might confer advantages within the invertebrate host.

D000818:Animals
D005786:Gene Expression Regulation
D015800:Protozoan Proteins
D034622:RNA Interference
D012333:RNA, Messenger
D016053:RNA, Protozoan
D016601:RNA-Binding Proteins
D059467:Transcriptome
D014346:Trypanosoma brucei brucei

Pumilio
Trypanosoma brucei
mRNA decay
translation


Interaction of insulin with colloidal ZnS quantum dots functionalized by various surface capping agents.

Abstract: Interaction of quantum dots (QDs) and proteins strongly influenced by the surface characteristics of the QDs at the protein-QD interface. For a precise control of these surface-related interactions, it is necessary to improve our understanding in this field. In this regard, in the present work, the interaction between the insulin and differently functionalized ZnS quantum dots (QDs) were studied. The ZnS QDs were functionalized with various functional groups of hydroxyl (OH), carboxyl (COOH), amine (NH2), and amino acid (COOH and NH2). The effect of surface hydrophobicity was also studied by changing the alkyl-chain lengths of mercaptocarboxylic acid capping agents. The interaction between insulin and the ZnS QDs were investigated by fluorescence quenching, synchronous fluorescence, circular dichroism (CD), and thermal aggregation techniques. The results reveal that among the studied QDs, mercaptosuccinic acid functionalized QDs has the strongest interaction (∆G°=-51.50kJ/mol at 310K) with insulin, mercaptoethanol functionalized QDs destabilize insulin by increasing the beta-sheet contents, and only cysteine functionalized QDs improves the insulin stability by increasing the alpha-helix contents of the protein, and. Our results also indicate that by increasing the alkyl-chain length of capping agents, due to an increase in hydrophobicity of the QDs surface, the beta-sheet contents of insulin increase which results in the enhancement of insulin instability.

Hosseinzadeh|Ghader|G|
Maghari|Ali|A|
Farniya|Seyed Morteza Famil|SMF|
Keihan|Amir Homayoun|AH|
Moosavi-Movahedi|Ali A|AA|

D002942:Circular Dichroism
D007328:Insulin
D045663:Quantum Dots
D013050:Spectrometry, Fluorescence
D013440:Sulfides
D017967:Zinc Compounds

Insulin
ZnS
Quantum dots
Capping agent
Denaturation


Simultaneous pancreas/kidney transplant recipients are predisposed to tissue-invasive cytomegalovirus disease and concomitant infectious complications.

Abstract:
BACKGROUND
Infections have increased in simultaneous pancreas/kidney transplant recipients (SPKTRs) with cytomegalovirus (CMV) infection being the most important viral infection with adverse impact on patient and allograft outcomes.

METHODS
We studied all primary SPKTRs and deceased-donor kidney transplant recipients (KTRs) between 2008 and 2015 for the development of CMV infection. A total of 21/62 SPKTRs (33.9%) and 90/335 KTRs (26.9%) were diagnosed with CMV infection. A control group of 41 SPKTRs without CMV infection was used for comparison.

RESULTS
SPKTRs showed an increased incidence of CMV infection compared with KTRs. SPKTRs were more likely to develop CMV disease, CMV pneumonia, recurrent CMV infection, higher initial and peak CMV loads, and more need for intravenous antiviral therapy compared with KTRs (P<.05). High-risk CMV serostatus (D+R-) and 2 HLA-B/-DR mismatches increased the risk of CMV infection in SPKTRs (P<.05). No differences were observed for patient and allograft outcomes (P>.05). SPKTRs with CMV infection were more likely to show concomitant Epstein-Barr virus (EBV) viremia compared with SPKTRs without CMV infection (P<.05). SPKTRs with CMV infection showed higher incidences of concomitant BK polyomavirus-associated nephropathy, EBV viremia, and sepsis compared with KTRs with CMV infection (P<.05).

CONCLUSION
Our results suggest a higher incidence and more severe course of CMV infection in SPKTRs compared with KTRs. The increased incidence of concomitant infectious complications among SPKTRs with CMV infection suggests an overall impaired immunity, and calls for more intense screening.


Modeling Varicella Zoster Virus Persistence and Reactivation - Closer to Resolving a Perplexing Persistent State.

Abstract: The latent state of the human herpesvirus varicella zoster virus (VZV) has remained enigmatic and controversial. While it is well substantiated that VZV persistence is established in neurons after the primary infection (varicella or chickenpox), we know little of the types of neurons harboring latent virus genomes, if all can potentially reactivate, what exactly drives the reactivation process, and the role of immunity in the control of latency. Viral gene expression during latency has been particularly difficult to resolve, although very recent advances indicate that it is more restrictive than was once thought. We do not yet understand how genes expressed in latency function in the maintenance and reactivation processes. Model systems of latency are needed to pursue these questions. This has been especially challenging for VZV because the development of in vivo models of VZV infection has proven difficult. Given that up to one third of the population will clinically reactivate VZV to develop herpes zoster (shingles) and suffer from its common long term problematic sequelae, there is still a need for both in vivo and in vitro model systems. This review will summarize the evolution of models of VZV persistence and address insights that have arisen from the establishment of new in vitro human neuron culture systems that not only harbor a latent state, but permit experimental reactivation and renewed virus production. These models will be discussed in light of the recent data gleaned from the study of VZV latency in human cadaver ganglia.

Laemmle|Lillian|L|
Goldstein|Ronald S|RS|
Kinchington|Paul R|PR|

varicella zoster virus
reactivation
latency
animal models
human neuron culture models


Unexpected Serotonin Syndrome, Epileptic Seizures, and Cerebral Edema Following 2,5-dimethoxy-4-bromophenethylamine Ingestion.

Abstract: 4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a designer drug. In Europe, 2C-B is easily obtained and used for recreational purposes. It is known for its stimulating effects similar to those of 3,4-methylenedioxymethamphetamine, although in higher doses it has more hallucinogenic effects. Here, we report a case of 2C-B ingestion, confirmed by liquid chromatography-tandem mass spectrometry, in an 18-year-old man. The neurological consequences were severe, including the development of serotonin syndrome and severe brain edema. Supportive therapy resulted in a stable condition, although, after several months, the patient still suffered from severe neurological impairment due to the drug-induced toxicity. This case showed that 2C-B could not be identified with the drugs of abuse screening routinely used in Dutch hospitals. The use of 2C-B carries many risks, with potentially profound neurological damage, that both consumers and healthcare physicians are unaware of.

Spoelder|Antoinette S|AS|
Louwerens|Jan K G|JKG|
Krens|Stefanie D|SD|
Jager|Nynke|N|
LeCouffe|Natalie E|NE|
de Ruijter|Wouter|W|
Brunt|Tibor M|TM|

serotonin syndrome
2C-B
designer drugs
forensic science
intoxication
phenethylamine


Pre-Anticipatory Anxiety and Autonomic Nervous System Response to Two Unique Fitness Competition Workouts.

Abstract: To evaluate the feasibility of on-site collection of subjective anxiety, autonomic nervous system activity, and salivary catecholamines surrounding high-intensity functional training (HIFT) competition, ten experienced HIFT competitors completed baseline assessments of anxiety and heart rate variability (HRV). Then, in two consecutive weeks (Workout 1 and 2) within the competition, HRV was recorded and examined in 5-min segments prior to exercise (PRE) and across a 30-min period after competitors completed their choice of the prescribed or scaled each workout. Subjective anxiety ratings and saliva samples were collected at PRE and immediately-(IP), 30-min (30P), and 60-min post-exercise (60P). Saliva samples were analyzed for concentrations of epinephrine and norepinephrine. Generalized linear mixed models with repeated measures revealed significant (p < 0.05) differences between workouts for all measures. Compared to Workout 1, anxiety (~50%), epinephrine (173-340%), norepinephrine (29-234%) were greater in Workout 2 and various HRV-derived indices were more depressed. Additionally, some HRV-derived indices appeared to be modulated (p < 0.05) by competitive level and sex at PRE and throughout the 30-min recovery period. These data suggest that autonomic activity may differ between the competitive and laboratory settings, and that the response may be further modulated by the workout's design, the athlete's sex, and competitive level.

catecholamines
high-intensity functional training
heart rate variability
CrossFit
recreational athletes


Predominance of M2 macrophages in gliomas leads to the suppression of local and systemic immunity.

Abstract: Glioblastoma is a highly prevalent and aggressive form of primary brain tumor. It represents approximately 56% of all the newly diagnosed gliomas. Macrophages are one of the major constituents of tumor-infiltrating immune cells in the human gliomas. The role of immunosuppressive macrophages is very well documented in correlation with the poor prognosis of patients suffering from breast, prostate, bladder and cervical cancers. The current study highlights the correlation between the tumor-associated macrophage phenotypes and glioma progression. We observed an increase in the pool of M2 macrophages in high-grade gliomas, as confirmed by their CD68 and CD163 double-positive phenotype. In contrast, less M1 macrophages were noticed in high-grade gliomas, as evidenced by the down-regulation in the expression of CCL3 marker. In addition, we observed that higher gene expression ratio of CD163/CCL3 is associated with glioma progression. The Kaplan-Meier survival plots indicate that glioma patients with lower expression of M2c marker (CD163), and higher expression of M1 marker (CCL3) had better survival. Furthermore, we examined the systemic immune response in the peripheral blood and noted a predominance of M2 macrophages, myeloid-derived suppressor cells and PD-1+ CD4 T cells in glioma patients. Thus, the study indicates a high gene expression ratio of CD163/CCL3 in high-grade gliomas as compared to low-grade gliomas and significantly elevated frequency of M2 macrophages and PD-1+ CD4 T cells in the blood of tumor patients. These parameters could be used as an indicator of the early diagnosis and prognosis of the disease.

Vidyarthi|Aurobind|A|
Agnihotri|Tapan|T|
Khan|Nargis|N|
Singh|Sanpreet|S|
Tewari|Manoj K|MK|
Radotra|Bishan D|BD|
Chatterjee|Deepyan|D|
Agrewala|Javed N|JN|

D015972:Gene Expression Regulation, Neoplastic

D061026:Programmed Cell Death 1 Receptor


Childhood GPA, EGPA, and MPA.

Abstract: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a term used to describe rare primary systemic vasculitides affecting small and medium-sized blood vessels. AAV diseases which include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), Microscopic Polyangiitis (MPA) and renal limited ANCA vasculitis. These multisystemic disorders involve upper and lower respiratory tract and kidneys associated with organ damage and long term sequelae. Newer understanding of pathogenesis in AAV have paved the way for clinical research with different biologic therapies. In spite of the paucity of clinical trials in pediatric AAV, the long-term survival of patients with AAV has improved dramatically. International collaborations will help to conduct clinical trials in pediatric AAV and help in better understanding of remission rates, relapse rates, and other outcomes. This article aims to provide a comprehensive review of pediatric AAV with a focus on epidemiology, disease pathogenesis, treatment trials, and prognosis.

D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

ANCA
ANCA associated vasculitis
Childhood vasculitis


Long-term effects of malnutrition on early-life famine survivors and their offspring: New evidence from the Great Vietnam Famine 1944-45.

Abstract: We investigate the long-term effects of the 1944-45 Great Vietnam Famine on early-life survivors and their offspring using census data, household survey data and historical administrative data. Unlike previous famine studies, we measure famine severity using a unique, more direct, and "plausibly exogenous" metric of food availability: province-level excess paddy (rice) production per capita in 1944. Our study makes two novel contributions. First, we overcome several selection problems associated with the estimation of true famine effects, given the short duration and spatial variation of the Vietnamese famine. Second, we investigate the intergenerational effects of famine, focusing specifically on the occupation of the survivors' parents and the school participation of the survivors' offspring. Our preferred specification estimates generalized triple differences that allow us to control for birth-year and birth-province fixed effects and nation-wide shocks. Our findings suggest that the Vietnamese famine reduced literacy by around 3 percent, BMI by 5.6%-8.4%, arm-length by 4.5%-6.7% (1.1-1.7 cm), height by 2.2%-3.2% (3.4-5 cm), and weight by 10%-14% (4.7-6.9 kg) among the affected cohort. These detrimental famine effects also extended to economic welfare, in the form of lower household incomes and lower non-food household expenditures in adulthood. We also document a 4.9%-7.2% reduction in school participation among survivors' offspring, which has major implications for the exogenous origins of social mobility, inequality, and poverty.

Guven|Cahit|C|0000-0001-8346-772X
Hoang|Trung|T|
Rahman|Muhammad H|MH|
Ulubaşoğlu|Mehmet A|MA|

famine
Vietnam
health
human capital
intergenerational transmission


Alginate microbead-encapsulated silver complexes for selective delivery of broad-spectrum silver-based microbicides.

Abstract: In sub-Saharan Africa, human immunodeficiency virus (HIV) infections are predominantly acquired via heterosexual contact, and women are at greatest risk of being infected. This region also has the highest rates of sexually transmitted infections (STIs) per capita worldwide; STIs are strongly associated with increased HIV transmission. Therefore, there is an urgent requirement for microbicides that are active against HIV and STIs. Silver compounds exhibit broad antimicrobial activity, making them potentially ideal broad-spectrum microbicides. However, for silver compounds to be effective microbicides, they must be active within seminal fluid and the delivery vehicle used must protect the silver microbicide from vaginal fluid components but selectively release it during intercourse and/or following ejaculation. In this study, silver complexes were synthesised from the ligands saccharin, benzimidazole and 8-hydroxyquinoline and their microbicidal activity was assessed. We show that a silver saccharinate-benzimidazole complex (AgSB) exhibited activity against HIV-1, herpes simplex virus type 2 (HSV-2) and Neisseria gonorrhoeae at concentrations significantly below LD(50) levels for the vaginal mucosal cell line SiHa. Furthermore, we show that alginate microbeads are stable in vaginal fluid simulant but rapidly dissolve in seminal fluid simulant. Finally, we have established that microbead-encapsulated AgSB, dissolved in seminal fluid simulant, is active against the above pathogens, albeit at higher concentrations for HIV-1. This research therefore highlights, for the first time, the potential use of silver complexes encapsulated in alginate microbeads as a novel system for the delivery and selective release of broad-spectrum silver-based microbicides within the vaginal milieu during sexual intercourse/after ejaculation.

Damelin|Leonard H|LH|
Fernandes|Manuel A|MA|
Tiemessen|Caroline T|CT|

Alginate Silver Microbicide HIV STI HSV-2


The impact of ICAM-1, CCL2 and TGM2 gene polymorphisms on differentiation syndrome in acute promyelocytic leukemia.

Abstract:
BACKGROUND
Although arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are well-tolerated and effective treatments for Acute Promyelocytic Leukemia (APL), Differentiation Syndrome (DS) is a lethal side effect in some patients. The pathogenesis of DS is complex and not well understood; however, it is considered as an inflammatory response due to cytokines release of differentiated cells. Moreover, adhesion molecules that are widely expressed on the surface of differentiated cells and gene expression changes of transglutaminase2 (TGM2) are mechanisms involved in the development of DS. The purpose of this study was to assess the association of single nucleotide polymorphisms (SNP) of Intercellular Adhesion Molecule-1 (ICAM-1), chemokine (C-C motif) ligand 2 (CCL2) and TGM2 as inflammatory factors with differentiation syndrome susceptibility.

METHODS
DNA was extracted from 133 APL patients and 100 normal controls. Assessment according to the PETHEMA criteria revealed that 13.5% of these patients experienced differentiation syndrome. Tetra-ARMS PCR and PCR-RFLP were done to amplify DNA fragments in APL patients with and without DS. Then DNA sequencing was done to validate the results. SNPStats, SPSS and Finch TV were used to analyze the results.

RESULTS
A significant correlation was found between rs4811528 in the TGM2 gene and differentiation syndrome susceptibility (P = 0.002, 95% CI = 1.74-18.81, OR = 5.72) while rs5498 in ICAM-1, rs1024611 in CCL2, and rs7270785 in TGM2 genes showed no correlation with differentiation syndrome. The G allele of rs7270785 and rs4811528 showed a haplotypic association with differentiation syndrome (P = 0.03, 95% CI = 1.13-13.86, OR = 3.96).

CONCLUSIONS
AA genotype of the TGM2 SNP (rs4811528) may be a risk factor for development of DS in patients with APL following the use of ATRA/ATO.

Mohammadzadeh|Zahra|Z|
Omidkhoda|Azadeh|A|
Chahardouli|Bahram|B|
Hoseinzadeh|Ghazaleh|G|
Moghaddam|Kamran Ali|KA|
Mousavi|Seyed Asadollah|SA|
Rostami|Shahrbano|S|

D000091345:Protein Glutamine gamma Glutamyltransferase 2

D018746:Systemic Inflammatory Response Syndrome

ICAM-1
Differentiation syndrome
Acute Promyelocytic leukemia
SNPs
CCL2 chemokine
Transglutaminase II


The impact of transitioning from availability of outside records within electronic health records to integration of local and outside records within electronic health records.

Abstract:
OBJECTIVE
While there has been a substantial increase in health information exchange, levels of outside records use by frontline providers are low. We assessed whether integration between outside data and local data results in increased viewing of outside records, overall and by encounter, provider, and patient type.

MATERIALS AND METHODS
Using data from UCSF Health, we measured change in outside record views after integrating the list of local (UCSF) and outside (other health systems on Epic [Epic Systems, Verona, WI]) encounters on the Chart Review tab. Previously, providers only viewed records from outside encounters on a separate tab. We used an interrupted time series design (with outside record viewing event counts aggregated to the week level) to measure changes in the level and trend over a 1-year period.

RESULTS
There was a large increase in the level of outside record views of 22 920 per week (P < .001). The change in trend went from a weekly increase of 116 (P < .05) to a decrease of 402 (P = .08), reflecting a small effect decay. There were increases in the level of views for all provider and encounter types: attendings (n = 3675), residents (n = 3277), and nurses (n = 914); and inpatient (n = 1676), emergency (n = 487), and outpatient (n = 7228) (P < .001 for all). Results persisted when adjusted for total encounter volume.

DISCUSSION
While outside records were readily available before the encounter integration, the simple step of clicking on a separate tab appears to have depressed use.

CONCLUSIONS
User interface designs that comingle local and outside data result in higher levels of viewing and should be more broadly pursued.

D019033:Delivery of Health Care, Integrated

D065186:Interrupted Time Series Analysis

audit log
data integration
interoperability


Cardiovascular correlates of human emotional vasovagal syncope differ from those of animal freezing and tonic immobility.

Abstract: It has been suggested that vertebrate freezing and tonic immobility (TI) represent the antecedents of human emotional vasovagal syncope. When a prey detects an approaching predator, it suddenly interrupts its ongoing activity and behaves according to the predator's distance. A prey enters TI when the fight or flight reaction is not feasible and the animal is captured. TI is defined as a post-contact, all or none, innate immobility reflex response that persists after the end of the prey-predator contact. In humans, vasovagal syncope, a reversible adaptive response frequently associated with fainting, occurs in response to emergency conditions such as strong emotions, orthostatic stress, anoxia, visceral pain and decrease in blood volume. The aim of the present review is to dispute the hypothesis that human vasovagal syncope represents the evolution of the bradycardia observed during freezing in a prey-predator condition in other vertebrates. The hypothesis does not take into account three crucial issues: 1) freezing and TI are defence responses which differ from each other in behavioural, cardiovascular and neurophysiological correlates; 2) the initial phase of vasovagal syncope is associated with tachycardia, whereas freezing is associated with a sudden fast-developing bradycardia; 3) the second phase of vasovagal syncope terminates with a blood pressure collapse, whereas blood pressure levels remain at basal levels during both freezing and TI.

Vasovagal syncope
Freezing
Tonic immobility
Blood pressure
Animal models
Heart rate


Clinical impact of gastroesophageal reflux disease in patients with subacute/chronic cough.

Abstract:
BACKGROUND
While gastroesophageal reflux disease (GERD) is one of the commonest causes of subacute/chronic cough along with cough-variant asthma (CVA) and rhinosinusitis, its clinical impact remains unknown. Therefore, we sought to investigate the impact of GERD in patients with subacute/chronic cough.

METHODS
Between April 2012 and March 2018, a total of 312 patients presenting subacute or chronic cough lasting for ≥3 weeks [median cough duration, 4.9 (0.7-434) months] underwent diagnostic tests. GERD symptoms and cough-specific QoL were evaluated through the Frequency Scale for Symptoms of Gastroesophageal reflux (FSSG) and the Japanese version of the Leicester Cough Questionnaire (J-LCQ). According to the FSSG domains, patients with GERD were arbitrarily categorized into 3 groups; acid-reflux predominant, dysmotility predominant, and pauci-symptoms groups, respectively.

RESULTS
The average scores of J-LCQ was 12.5 (SD3.7). One hundred-forty three were diagnosed as having GERD-related cough based on classical reflux symptoms including heartburn and characteristic triggers of cough such as phonation, rinsing, lying, and eating. Most of them (89.8%) had other causative diseases including CVA. Cough lasted longer (p = 0.019) and required a longer time until alleviation (p = 0.003) in patients with GERD than in those without GERD. They also scored lower J-LCQ than counterpart group (p < 0.0001). In terms of symptom stratification, dysmotility predominant group showed significant more response to specific GERD treatments than the remnants (p = 0.002).

CONCLUSIONS
These results indicate that GERD is associated with the aggravation of other causes including CVA. Particularly, dysmotility symptoms may be potential therapeutic target for GERD-related cough.

Kanemitsu|Yoshihiro|Y| Kurokawa|Ryota|R| Takeda|Norihisa|N| Takemura|Masaya|M| Fukumitsu|Kensuke|K| Asano|Takamitsu|T| Yap|Jennifer|J| Suzuki|Motohiko|M| Fukuda|Satoshi|S| Ohkubo|Hirotsugu|H| Maeno|Ken|K| Ito|Yutaka|Y| Oguri|Tetsuya|T| Niimi|Akio|A|

Gastroesophageal reflux disease
Subacute/chronic cough
GERD symptoms
Cough-specific quality of life
Prokinetic agents


Working memory training revisited: A multi-level meta-analysis of n-back training studies.

Abstract: The efficacy of working memory (WM) training has been a controversial and hotly debated issue during the past years. Despite a large number of training studies and several meta-analyses, the matter has not yet been solved. We conducted a multi-level meta-analysis on the cognitive transfer effects in healthy adults who have been administered WM updating training with n-back tasks, the most common experimental WM training paradigm. Thanks to this methodological approach that has not been employed in previous meta-analyses in this field, we were able to include effect sizes from all relevant tasks used in the original studies. Altogether 203 effect sizes were derived from 33 published, randomized, controlled trials. In contrast to earlier meta-analyses, we separated task-specific transfer (here untrained n-back tasks) from other WM transfer tasks. Two additional cognitive domains of transfer that we analyzed consisted of fluid intelligence (Gf) and cognitive control tasks. A medium-sized transfer effect was observed to untrained n-back tasks. For other WM tasks, Gf, and cognitive control, the effect sizes were of similar size and very small. Moderator analyses showed no effects of age, training dose, training type (single vs. dual), or WM and Gf transfer task contents (verbal vs. visuospatial). We conclude that a substantial part of transfer following WM training with the n-back task is task-specific and discuss the implications of the results to WM training research.

Soveri|Anna|A| Antfolk|Jan|J| Karlsson|Linda|L| Salo|Benny|B| Laine|Matti|M|

Working memory
Meta-analysis
N-back
Cognitive training
Executive functions


Dysphagia Rehabilitation: Similarities and Differences in Three Areas of the World.

Abstract: Although the goal of dysphagia rehabilitation is the same, population needs, clinical practice patterns, availability of resources, and dysphagia research varies greatly around the world. The goal of this review is to introduce the reader to the context in which dysphagia rehabilitation is practiced, to describe practice patterns, and to highlight the dysphagia research being performed in three distinct regions of the world: North America, New Zealand and Australia, and Japan.

González-Fernández|Marlís|M|
Huckabee|Maggi-Lee|ML|
Doeltgen|Sebastian H|SH|
Inamoto|Yoko|Y|
Kagaya|Hitoshi|H|
Saitoh|Eichii|E|

Dysphagia practice evaluation management screening swallowing


Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa.

Abstract:
OBJECTIVE
Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM.

DESIGN
Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers.

RESULTS
We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury.

CONCLUSION
Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.

mucosal injury
gastric epithelial cell function
gastric metaplasia


The relationship of plasma Trans fatty acids with dietary inflammatory index among US adults.

Abstract:
BACKGROUND
It has been suggested that trans fatty acids (TFAs) play an important role in cardiovascular diseases. We investigated the association between plasma TFAs and the dietary inflammatory index (DII) ™ in US adults.

METHODS
National Health and Nutrition Examination Survey (NHANES) participants with data on plasma TFAs measured from 1999 to 2010 were included. Energy-adjusted-DII ™ (E-DII ™) expressed per 1000 kcal was calculated from 24-h dietary recalls. All statistical analyses accounted for the survey design and sample weights.

RESULTS
Of the 5446 eligible participants, 46.8% (n = 2550) were men. The mean age of the population was 47.1 years overall, 47.8 years for men and 46.5 years for women (p = 0.09). After adjustment for C-reactive protein, body-mass-index, smoking, race, age, education, and marital status in linear regressions, trans 9-hexadecenoic acid [β coefficient 0.068 (95% CI: 0.032 to 0.188)], trans 11-octadecenoic acid [β coefficient 0.143 (95% CI: 0.155 to 0.310)], trans 9-octadecenoic acid [β coefficient 0.122 (95% CI: 0.120 to 0.277)], trans 9, and trans 12-octadienoic acid [β coefficient 0.103 (95% CI: 0.090 to 0.247)] were positively associated with the DII (all p < 0.001).

CONCLUSION
The association of plasma TFAs with a marker of dietary inflammation suggests an underlying mechanism in the initiation and progression of cardiovascular diseases.

Mazidi|Mohsen|M|
Gao|Hong-Kai|HK|
Shivappa|Nitin|N|
Wirth|Michael D|MD|
Hebert|James R|JR|
Kengne|Andre Pascal|AP|

National Health and nutrition examination survey


Protective Effects of Small-Molecule Oligopeptides Isolated from Tilapia Fish Scale on Ethanol-Induced Gastroduodenal Injury in Rats.

Abstract: Peptic ulcer has a serious impact on people's health around the world, and traditional medicines can cause adverse reactions. This study investigated the protective effects of tilapia collagen oligopeptides (TCOPs) on gastroduodenal injury. Seventy-two specific pathogen-free (SPF) male Sprague Dawley (SD) rats were randomly divided into six groups according to body weight: normal control group, ethanol group, whey protein group (500 mg/kg BW), and three TCOPs dose groups (250, 500, 1000 mg/kg BW). After intragastric administration for 30 days, the acute gastroduodenal injury was induced by anhydrous ethanol (5 mL/kg, intragastrically) in all groups except the normal control group. Biomarkers in gastric and duodenal tissue and serum were measured. Furthermore, western blot was used to detect the expression of apoptosis-related proteins. The results showed that the administration with TCOPs significantly reduced gastric and duodenal ulcer index, increased gastric juice pH, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, along with the reduction of malondialdehyde (MDA) contents. TCOPs decreased tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and myeloperoxidase (MPO) levels, while interleukin- 10 (IL-10) levels were increased. Furthermore, pepsinogens 1 (PG1), pepsinogens 2 (PG2), gastrin (GAS), and the pepsinogen ratio (PGR) were decreased, the prostaglandin E2 (PGE2) and NO contents were increased after TCOPs intervention. Moreover, TCOPs up-regulated the expression of Bcl-2 and inhibited the expression of Bax and Caspase-3. In conclusion, TCOPs have protective effects on ethanol-induced gastroduodenal injury through gastrointestinal mucosal microcirculation promotion, antioxidation, anti-inflammation, and anti-apoptosis mechanisms.

Hu|Jiani|J|0000-0003-1733-6822 Liu|Rui|R| Yu|Xiaochen|X| Li|Zhen|Z| Liu|Xinran|X| Hao|Yuntao|Y| Zhu|Na|N| Kang|Jiawei|J| Li|Yong|Y|

gastroduodenal injury
tilapia collagen oligopeptides
antioxidant
anti-inflammation
anti-apoptosis


Birds, meat, and babies: the multiple realities of fetuses in Qatar.

Abstract: This paper explores miscarriage in a variety of Qatari contexts to reveal the multiple realities of the unborn. During 18 months of ethnographic research, a range of settings in which fetuses emerged were explored. The unborn are represented and imagined differently, particularly in relation to the ways they are located, with multiple beings emerging according to the context and position of the stakeholder. This paper considers fetuses produced within these contexts and considers how they can be different beings simultaneously. The paper reveals how categories meant to define these beings are in flux and are constantly negotiated; it reflects moments of ambiguity. The paper serves as an illustration of the way in which value-afforded pregnancy materials affects the contexts in which they emerge; this then loops back as context dictates the significance of the material, hence multiple realities of these beings.

multiple
Qatar
miscarriage
medical anthropology
reproduction


Hydration by colonic enteroclysis: An alternative to parenteral hydration in patients with high-output double enterostomy.

Abstract:
BACKGROUND
High-output double enterostomies (DESs) result in sodium and fluid loss responsible for frequent episodes of dehydration and hospitalizations. Hydration by enteroclysis (HE) is an alternative to parenteral hydration when the small bowel, or the downstream colon, is accessible and functional.

METHODS
A retrospective analysis was conducted on all consecutive patients admitted in our institution with high-output (≥1200 ml per 24 h) DES and access to downstream intestine (including colon), who were treated by enteroclysis between 2015 and 2019. A sodium chloride and bicarbonate solution was instilled through a tube inserted in the colon. The objectives were diuresis >1 L, natriuresis >40 mmol/24 h, and urinary sodium-to-potassium ratio >1.

RESULTS
HE was conducted in 52 patients (24 female, 28 male). Initially, 30 patients received intravenous support. Fifteen patients (50%) were weaned from all parenteral support, of whom 11 of 12 (92%) received fluid and electrolyte support and 4 of 18 (22%) received parenteral nutrition (PN). When intravenous fluids were still required, daily volumes decreased from 2714 ± 1424 to 1578 ± 1000 ml per 24 h (P = .001), as did the energetic intake (NS), from 1439 ± 556 to 1230 ± 362 kcal per 24 h (P = .096).

CONCLUSION
HE through the efferent intestine limits the requirement for parenteral hydration in patients with high-output DES. For patients with intestinal failure dependent on PN, it reduces daily infused volumes.

hydration
enteroclysis
enterostomy
intravenous fluids
short-bowel syndrome


Stable W/O/W multiple nanoemulsion encapsulating natural tocotrienols and caffeic acid with cisplatin synergistically treated cancer cell lines (A549 and HEP G2) and reduced toxicity on normal cell line (HEK 293).

Abstract: This work aimed to evaluate the effects of encapsulated tocotrienols (TRF) and caffeic acid (CA) in water-in-oil-in-water (W/O/W) multiple nanoemulsion with cisplatin towards cancer cells. This work is important considering the limited efficacy of cisplatin due to tumour resistance, as well as its severe side effects. A549 and HEP G2 cancer cell lines were utilised for evaluating the efficacy of the encapsulated W/O/W while HEK 293 normal cell line was used for evaluating the toxicity. TRF, CA and CIS synergistically improved apoptosis in the late apoptotic phase in A549 and HEP G2 by 23.1% and 24.9%, respectively. The generation of ROS was enhanced using TRF:CA:CIS by 16.9% and 30.2% for A549 and HEP G2, respectively. Cell cycle analysis showed an enhanced cell arrest in the G0/G1 phase for both A549 and HEP G2. TRF, CA and CIS led to cell death in A549 and HEP G2. For HEK 293, ~33% cell viability was found when only CIS was used while >95% cell viability was observed when TRF, CA and CIS were used. This study demonstrates that the encapsulated TRF and CA in W/O/W with CIS synergistically improved therapeutic efficacy towards cancer cells, as well as lowered the toxicity effects towards normal cells.

Raviadaran|Revathi|R|
Ng|Mei Han|MH|
Chandran|Davannendran|D|
Ooi|Kah Kooi|KK|
Manickam|Sivakumar|S|

Nanoemulsion
Tocotrienols
Caffeic acid
Cancer
Double emulsion
Microfluidizer
Synergism
Ultrasound


Gender Differences in the Impact of Intergenerational Support on Depressive Symptoms among Older Adults in Korea.

Abstract: Background: This study examined the relationship between intergenerational support patterns and depressive symptoms among older men and women in Korea. Methods: A nationally representative survey of non-institutionalized, community-dwelling older adults in Korea was used. A total of 7531 older adults (3592 men and 3939 women) was included in the analysis. Results: We observed gender differences in the impact of financial support exchanges on depressive symptoms. A lack of mutual financial support significantly increased the risk of depressive symptoms by 3.83 times (95% CI 2.34-6.24) in men and 1.73 times (95% CI 1.06-2.83) in women. Men who received financial support were more likely to experience depressive symptoms (OR (Odds Ratio), 1.81, 95% CI 1.36-2.42), whereas women who provided financial support were more likely to experience depressive symptoms (OR 2.82, 95% CI 1.21-6.56). The lack of an exchange of emotional support was significantly associated with depressive symptoms in both men (OR 1.49, 95% CI 1.17-1.90) and women (OR 1.87, 95% CI 1.50-2.34). Conclusions: We discuss the evidence of gender differences in intergenerational support exchange patterns and their impact on depressive symptoms within the context of Korean cultures and suggest that future research should be conducted on gender differences in the impact of intergenerational support on mental health across diverse societies.

gender
depression
older adults
intergenerational relations
social support


Modeling cow somatic cell count using sensor data as input to generalized additive models.

Abstract: This research paper presents a study investigating if sensor data from an automatic milking rotary could be used to model cow somatic cell count (composite milk SCC: CMSCC). CMSCC is valuable for udder health monitoring and individual cow udder health surveillance could be improved by predicting CMSCC between routine samplings. Data regularly recorded in the automatic milking rotary, in one German dairy herd, were collected for analysis. The cows (Holstein-Friesian, n = 372) were milked twice daily and sampled once weekly in afternoon milkings for 8 weeks for CMSCC. From the potential independent variables, including quarter conductivity, milk flow, blood in milk, kick-offs, not milked quarters and incomplete milkings, new variables that combined quarter data were created. Past period records, i.e. lags, of up to seven days before the actual CMSCC sampling event were added in the dataset to investigate if they were of use in modeling the cell count. Univariable generalized additive models (GAM) were used to screen the data to select potential independent variables. Furthermore, several multivariable GAM were fitted in order to compare the importance of the potential independent variables and to explore how the model performance would be affected by using data from various number of days before the CMSCC sampling event. The result of the model selection showed that the best explanation of CMSCC was provided by the model incorporating all significant variables from the variable screening for the seven preceding days, including the day of the CMSCC sampling event. However, using data from only three days before the CMSCC sampling event is suggested to be sufficient to model CMSCC. Variables combining conductivity quarter data, together with quarter conductivity, are suggested to be important in describing CMSCC. We conclude that CMSCC can be modeled with a high degree of explanation using the information routinely recorded by the milking robot.

Anglart|Dorota|D| Hallén-Sandgren|Charlotte|C| Waldmann|Patrik|P| Wiedemann|Martin|M| Emanuelson|Ulf|U|

somatic cell count
Additive model
automatic milking rotary
udder health


Home care workers' experiences of work conditions related to their occupational health: a qualitative study.

Abstract:
BACKGROUND
The need for home care workers (HCWs) is rapidly growing in Norway due to the increasingly growing elderly population. HCWs are exposed to a number of occupational hazards and physically demanding work tasks. Musculoskeletal disorders, stress, exhaustion, high sick leave rates and a high probability of being granted a disability pension are common challenges. This qualitative study explored the views of HCWs on how working conditions affect their safety, health, and wellbeing.

METHODS
A descriptive and explorative design was utilised using semi-structured individual interviews with eight HCWs from three home care units in a middle-sized Norwegian city. Interviews were conducted in the Norwegian language, audio-recorded, and transcribed verbatim. The data was analysed by systematic text condensation. Key data quotes were translated into English by the authors.

RESULTS
HCWs reported that meaningful work-related interactions and relationships contributed to their improved wellbeing. Challenging interactions, such as verbal violence by consumers, were deemed stressful. The unpredictable work conditions HCWs encounter in users' homes contributed to their exposure to environmental hazards and unhealthy physical workloads. This was the case, although the employer promoted ergonomic work practices such as ergonomic body mechanics when mobilising and handling of clients, using safe patient handling equipment. HCWs perceived high level of individual responsibility for complying with company safety policies and practices, representing a health barrier for some. Organisational frameworks created unhealthy work conditions by shift work, time pressure and staffing challenges. Performing tasks in accordance with HCWs professional skills and identity was perceived as health-promoting.

CONCLUSIONS
This study suggests that unpredictable working conditions at users' home can adversely affect the safety, health, and wellbeing of HCWs. The interaction between the unpredictable environment at users' homes, HCWs' perceived high level of individual responsibility for complying with company safety policies and practices, and staffing challenges due to sickness-related absences upon the workplace creates tense work conditions with a negative influence on HCWs health.

Grasmo|Sunniva Grønoset|SG|
Liaset|Ingeborg Frostad|IF|
Redzovic|Skender Elez|SE|

Home care workers
Work conditions
Occupational health
Qualitative study
Home care services


Contrasting effects of warming and increased snowfall on Arctic tundra plant phenology over the past two decades.

Abstract: Recent changes in climate have led to significant shifts in phenology, with many studies demonstrating advanced phenology in response to warming temperatures. The rate of temperature change is especially high in the Arctic, but this is also where we have relatively little data on phenological changes and the processes driving these changes. In order to understand how Arctic plant species are likely to respond to future changes in climate, we monitored flowering phenology in response to both experimental and ambient warming for four widespread species in two habitat types over 21 years. We additionally used long-term environmental records to disentangle the effects of temperature increase and changes in snowmelt date on phenological patterns. While flowering occurred earlier in response to experimental warming, plants in unmanipulated plots showed no change or a delay in flowering over the 21-year period, despite more than 1 °C of ambient warming during that time. This counterintuitive result was likely due to significantly delayed snowmelt over the study period (0.05-0.2 days/yr) due to increased winter snowfall. The timing of snowmelt was a strong driver of flowering phenology for all species - especially for early-flowering species - while spring temperature was significantly related to flowering time only for later-flowering species. Despite significantly delayed flowering phenology, the timing of seed maturation showed no significant change over time, suggesting that warmer temperatures may promote more rapid seed development. The results of this study highlight the importance of understanding the specific environmental cues that drive species' phenological responses as well as the complex interactions between temperature and precipitation when forecasting phenology over the coming decades. As demonstrated here, the effects of altered snowmelt patterns can counter the effects of warmer temperatures, even to the point of generating phenological responses opposite to those predicted by warming alone.

Bjorkman|Anne D|AD|
Elmendorf|Sarah C|SC|
Beamish|Alison L|AL|
Vellend|Mark|M|
Henry|Gregory H R|GH|

Arctic tundra
plant phenology
flowering time
seed maturation
Bayesian hierarchical modeling
climate change
interval censoring


β-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer's Disease.

Abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a cascade of changes in cognitive, behavioral, and social activities. Several areas of the brain are involved in the regulation of memory. Of most importance are the amygdala and hippocampus. Antioxidant therapy is used for the palliative treatment of different degenerative diseases like diabetes, cirrhosis, and Parkinson's, etc. The objective of this study was to assess the effectiveness of exogenous antioxidants, in particular, β carotene (1.02 and 2.05 mg/kg) against intracerebroventricular injected streptozotocin-induced memory impairment in mice. Streptozotocin (3 mg/kg, i.c.v) was administered in two separate doses (on 1st and 3rd days of treatment) for neurodegeneration. Fifty Albino mice (male) were selected in the protocol, and they were classified into five groups (Group I-control, Group II-disease, Group III-standard, Group IV-V-β-carotene-treated) to investigate the cognitive enhancement effect of selected antioxidants. The cognitive performance was observed following the elevated plus-maze, passive avoidance, and open field paradigms. Acetylcholine esterase, β-amyloid protein, and biochemical markers of oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase were analyzed in brain homogenates. In silico activity against acetylcholinesterase (AChE) was determined by the molecular modeling of β-carotene. β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity. The in silico studies confirmed the binding capacity of β-carotene with the acetylcholinesterase enzyme. The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments. These results suggest that β-carotene could be useful for the treatment of neurodegenerative diseases such as Alzheimer's disease.

β-carotene
oxidative stress
biochemical markers
acetylcholinesterase
dementia


Duplex ultrasound versus CT angiography for the treatment planning of lower-limb arterial disease.

Abstract:
PURPOSE
This study aimed to assess the diagnostic accuracy of duplex sonography (DUS) compared with that of computed tomography angiography (CTA) in detecting occlusion and stenosis in peripheral arterial disease (PAD) in candidate patients for endovascular revascularization with intraprocedural digital subtraction angiography (DSA).

METHODS
The study involved 94 patients suffering from PAD who were candidates for endovascular procedures requiring DSA. They were all submitted preoperatively to DUS and CTA. Based on image analysis, five segments of the arterial tree were assessed: iliac, common femoral, superficial femoral, popliteal, and infrageniculate. According to the stenosis or occlusion degree, the arteries were rated as nonstenotic, stenotic, and occluded.

RESULTS
The agreement between DUS and CTA findings using DSA as a reference modality was expressed as a Cohen's kappa (κ) statistic agreement. Our results show that DUS has been less accurate than CTA in evaluating iliac arterial diseases (Cohen's κ agreement of 0.91 and 1.0, respectively) when measured against DSA. We found good diagnostic concordance between DUS and DSA in detecting hemodynamic stenosis and occlusion of the femoro-popliteal axis (Cohen's κ agreement between 0.96 and 0.93). Below the knee, CTA showed even less concordance with DSA (Cohen's κ 0.75).

CONCLUSIONS
Because of its accuracy, high-quality DUS performed by well-trained operators may therefore represent a good alternative to CTA in patients undergoing endovascular revascularization to minimize the use of contrast-enhanced radiological imaging. Nevertheless, preoperative CTA imaging is required in cases of nondiagnostic DUS or when a more complete overview of the vascular tree is needed for complex invasive interventions.

Duplex sonography (DUS)
Computed tomography angiography (CTA)
Peripheral arterial disease (PAD)
Endovascular revascularization
Digital subtraction angiography (DSA)


Lung squamous cell carcinoma with severe hypomagnesemia due to cisplatin plus gemcitabine in combination with necitumumab therapy: A case report.

Abstract: A 72-year-old man, diagnosed with advanced lung squamous cell carcinoma, was administered of cisplatin plus gemcitabine with necitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), as a sixth-line treatment. Tumor shrinkage was observed, but asymptomatic grade 4 hypomagnesemia occurred on day 8 of the second cycle. He received magnesium replenishment and hypomagnesemia recovered on day 40, but tumor progression was observed during the period of magnesium correction. Hypomagnesemia is known as a major adverse event of treatment with anti-EGFR antibodies, but there have been no case reports of severe hypomagnesemia or its clinical course.

Nakao|Akira|A|0000-0001-8308-4227 Inoue|Hiroyuki|H| Osaki|Yusuke|Y| Hirano|Ryosuke|R| Harada|Taishi|T| Aoyama|Takashi|T| Igata|Fumiyasu|F| Fujita|Masaki|M|

hypomagnesemia
cisplatin
gemcitabine
necitumumab
squamous cell lung cancer


The rise and fall of central dogmas.

Abstract: Stimulated by Francis Cricks "central dogma of molecular biology" open to criticism and rebuttal, five statements are formulated on current notions of tumor biology, inviting the criticism of the reader.

Malignant transformation
metastases
stroma
surveillance


Talimogene Laherparepvec in Advanced Mucosal Melanoma of the Urethra Upon Primary Resistance on Immune Checkpoint Inhibition: A Case Report.

Abstract: Background: Mucosal melanomas including melanomas of the urogenital tract represent a rare type of melanoma characterized by low mutational burden and poor prognosis. Immune checkpoint inhibition has so far only been assessed in a limited number of mucosal melanoma patients and, in contrast to response in cutaneous melanoma, was associated with disappointing response rates. The oncolytic viral immunotherapy Talimogene laherparepvec (T-VEC) has recently been approved for treatment of locally advanced or unresectable melanoma. T-VEC combines direct oncolytic effects with local and systemic immune-mediated anti-tumor response. Our rationale to use T-VEC in this case was an expected augmentation of immunogenicity by tumor lysis to overcome primary resistance of a mucosal melanoma to immune checkpoint blockade. Objective: To report the first case of an advanced mucosal melanoma of the urethra treated with intralesional application of Talimogene laherparepvec. Case Report: A 78-years old female patient was diagnosed with an advanced mucosal melanoma of the urethra with inguinal lymph node metastases and intravaginal mucosal metastases. Shortly after surgical resection of the tumor mass, intravaginal mucosal metastases, and new nodal metastases in proximity of the left iliac vessels were diagnosed. The patient was treated with the anti-PD1 antibody pembrolizumab and obtained a stable disease lasting for 30 weeks. However, upon checkpoint inhibition the patient developed a loco-regional progressive disease featuring bleeding intravaginal metastases, while nodal metastases remained stable. We stopped treatment with pembrolizumab and administered T-VEC directly into the intravaginal mucosal metastases. After five injections T-VEC yielded a partial response with clinical regression of the injected mucosal metastases. Disease remained stable for 16 weeks under biweekly T-VEC treatment. Thereafter the patient showed disease progression in nodal metastases. T-VEC was discontinued. Immunotherapy with pembrolizumab was restarted but failed to achieve a response. Finally, targeted therapy with imatinib was induced in presence of a druggable c-KIT mutation, leading to a considerable response of all tumor sites that is still ongoing. Conclusion: T-VEC represents an effective and well-tolerated treatment option for patients with loco-regionally advanced mucosal melanoma. In combination with immunotherapy, T-VEC bears the potential of synergistic effects to overcome the specific primary resistance of mucosal melanoma to immune checkpoint blockade.

Fröhlich|Anne|A|
Hoffmann|Friederike|F|
Niebel|Dennis|D|
Egger|Eva|E|
Kukuk|Guido M|GM|
Toma|Marieta|M|
Sirokay|Judith|J|
Bieber|Thomas|T|
Landsberg|Jennifer|J|

talimogene laherparepvec
mucosal melanoma
primary resistance
immune checkpoint blockade
intralesional treatment


Inhibition of Angiogenesis and Nitric Oxide Synthase (NOS), by Embelin & Vilangin Using in vitro, in vivo & in Silico Studies.

Abstract:
PURPOSE
In recent year's anti-angiogenesis agents have been recognized as effective drugs for the treatment of solid tumors, this prompted us to conduct the present study.

METHODS
The anti-angiogenic activity of dimeric form of embelin (vilangin) was evaluated using endothelial cell (in vitro) and chorioallantoic membrane (CAM) egg yolk angiogenesis model (in vivo) and in addition the docking behaviour of human nitric oxide synthases (NOS) with four different ligands was evaluated along with their putative binding sites using Discovery Studio Version 3.1 (in silico) compared with the parent compound (embelin).

RESULTS
Vilangin exhibits 50% cytotoxic at 92 ± 1 µg/ml concentration level with reference to ECV 304 endothelial cells. Both vilangin and embelin, showed inhibitory effects on wound healing, single cell migration, nitric oxide production, and endothelial ring formation at 0.1 and 1.0 µg/ml concentration level. Similarly, CAM assay also showed inhibitory effect of vilangin and embelin with respect their reduction in length, size and junctions of blood capillaries compared to untreated egg yolk. Docking studies and binding free energy calculations revealed that vilangin has maximum interaction energy (-74.6 kcal/mol) as compared to the other investigated ligands.

CONCLUSION
The results suggest that both vilangin and embelin attenuates angiogenesis in similar manner.

Narayanaswamy|Radhakrishnan|R|
Shymatak|Majumder|M|
Chatterjee|Suvro|S|
Wai|Lam Kok|LK|
Arumugam|Gnanamani|G|

Nitric oxide
Embelin
Vilangin
Wound healing
Endothelial ring formation
Egg yolk angiogenesis assay


Cell-Type Transcriptomes of the Multicellular Green Alga Volvox carteri Yield Insights into the Evolutionary Origins of Germ and Somatic Differentiation Programs.

Abstract: Germ-soma differentiation is a hallmark of complex multicellular organisms, yet its origins are not well understood. Volvox carteri is a simple multicellular green alga that has recently evolved a simple germ-soma dichotomy with only two cell-types: large germ cells called gonidia and small terminally differentiated somatic cells. Here, we provide a comprehensive characterization of the gonidial and somatic transcriptomes of V. carteri to uncover fundamental differences between the molecular and metabolic programming of these cell-types. We found extensive transcriptome differentiation between cell-types, with somatic cells expressing a more specialized program overrepresented in younger, lineage-specific genes, and gonidial cells expressing a more generalist program overrepresented in more ancient genes that shared striking overlap with stem cell-specific genes from animals and land plants. Directed analyses of different pathways revealed a strong dichotomy between cell-types with gonidial cells expressing growth-related genes and somatic cells expressing an altruistic metabolic program geared toward the assembly of flagella, which support organismal motility, and the conversion of storage carbon to sugars, which act as donors for production of extracellular matrix (ECM) glycoproteins whose secretion enables massive organismal expansion. V. carteri orthologs of diurnally controlled genes from C. reinhardtii, a single-celled relative, were analyzed for cell-type distribution and found to be strongly partitioned, with expression of dark-phase genes overrepresented in somatic cells and light-phase genes overrepresented in gonidial cells- a result that is consistent with cell-type programs in V. carteri arising by cooption of temporal regulons in a unicellular ancestor. Together, our findings reveal fundamental molecular, metabolic, and evolutionary mechanisms that underlie the origins of germ-soma differentiation in V. carteri and provide a template for understanding the acquisition of germ-soma differentiation in other multicellular lineages.

Matt|Gavriel Y|GY|
Umen|James G|JG|0000-0003-4094-9045

multicellularity
green algae
flagella
extracellular matrix
cooption
basal bodies
carbon metabolism
cell differentiation
evolution
photosynthesis
secretory pathway
senescence
stem cells


In Silico Typing of Classical and Non-classical HLA Alleles from Standard RNA-Seq Reads.

Abstract: Next-Generation Sequencing (NGS) enables the rapid generation of billions of short nucleic acid sequence fragments (i.e., "sequencing reads"). Especially, the adoption of gene expression profiling using whole transcriptome sequencing (i.e., "RNA-Seq") has been rapid. Here, we describe an in silico method, seq2HLA, that takes standard RNA-Seq reads as input and determines a sample's (classical and non-classical) HLA class I and class II types as well as HLA expression. We demonstrate the application of seq2HLA using publicly available RNA-Seq data from the Burkitt's lymphoma cell line DAUDI and the choriocarcinoma cell line JEG-3.

Boegel|Sebastian|S|
Bukur|Thomas|T|
Castle|John C|JC|
Sahin|Ugur|U|

D015395:Histocompatibility Antigens Class I

D000949:Histocompatibility Antigens Class II

In silico
RNA-Seq
NGS
HLA expression
HLA type
Immunoinformatics
Non-classical HLA class I


Detection and management of the first human anthrax outbreak in Togo.

Abstract:
OBJECTIVE
The aim of this study was to describe and define an outbreak of human anthrax in two villages in the northern savannah region of Togo.

PATIENTS AND METHOD
In December 2009, localised groups of deaths occurred among villagers and their livestock, confirmed to be due to anthrax at the district hospital of Dapaong in Northern Togo. The National Disease Control department undertook an investigation to describe the epidemiological, clinical and bacteriological characteristics of this outbreak.

RESULTS
Thirty-four individuals presented with clinical manifestations of anthrax. All patients were known to have consumed meat from cattle who had died of unknown causes or had been killed as a result of unknown illness. All patients presented with muco-cutaneous lesions; some had gastro-intestinal, neurological or meningeal symptoms, or septicaemia. One patient was co-infected with Plasmodium falciparum. Six deaths (17.6%) were reported at the beginning of the epidemic; 28 patients were successfully treated with a 10-day course of intravenous Penicillin or oral Amoxicillin. The two factors that contributed to the ultimate resolution of the anthrax outbreak were the increase of community awareness toward health promotion and vaccination of all farm animals.

CONCLUSION
Although six deaths occurred among families' members who were infected, new human anthrax cases were prevented by rapid treatment of victims as well as aggressive public health interventions. However the risk of re-emergence of infection and exposure still exists as there are no existing epidemiological mapping and no identification of infected zones; and furthermore, no functional anthrax surveillance system exists in the affected region.

Patassi|Akouda Akessiwe|AA|
Saka|Bayaki|B|
Landoh|Dadja Essoya|DE|
Agbenoko|Kodjo|K|
Tamekloe|Tsidi|T|
Salmon-Ceron|Dominique|D|


Molecular Genetics of Beauveria bassiana Infection of Insects.

Abstract: Research on the insect pathogenic filamentous fungus, Beauveria bassiana has witnessed significant growth in recent years from mainly physiological studies related to its insect biological control potential, to addressing fundamental questions regarding the underlying molecular mechanisms of fungal development and virulence. This has been in part due to a confluence of robust genetic tools and genomic resources for the fungus, and recognition of expanded ecological interactions with which the fungus engages. Beauveria bassiana is a broad host range insect pathogen that has the ability to form intimate symbiotic relationships with plants. Indeed, there is an increasing realization that the latter may be the predominant environmental interaction in which the fungus participates, and that insect parasitism may be an opportunist lifestyle evolved due to the carbon- and nitrogen-rich resources present in insect bodies. Here, we will review progress on the molecular genetics of B. bassiana, which has largely been directed toward identifying genetic pathways involved in stress response and virulence assumed to have practical applications in improving the insect control potential of the fungus. Important strides have also been made in understanding aspects of B. bassiana development. Finally, although increasingly apparent in a number of studies, there is a need for progressing beyond phenotypic mutant characterization to sufficiently investigate the molecular mechanisms underlying B. bassiana's unique and diverse lifestyles as saprophyte, insect pathogen, and plant mutualist.

D015966:Gene Expression Regulation, Fungal

Molecular genetics
Beauveria bassiana
Virulence
Stress response
Cuticle degradation
Fungal development and biology
Insect pathology
Signal transduction


Expansion of CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption.

Abstract:
OBJECTIVE
Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.

SUBJECTS
67 CD-1 mice and in vitro MDSC cultures.

TREATMENT
Adjuvant arthritis was induced by a subdermal injection of complete Freund's adjuvant. LN was induced by illumination of 750 lx at night.

METHODS
Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used.

RESULTS
Increased levels of splenic CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b+Ly6Ghigh expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN.

CONCLUSIONS
Our study raises the possibility that CD11b+Ly6Ghigh and CD11b+CD49d+ MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

Perfilyeva|Yuliya V|YV|
Abdolla|Nurshat|N|
Ostapchuk|Yekaterina O|YO|
Tleulieva|Raikhan|R|
Krasnoshtanov|Vladimir C|VC|
Belyaev|Nikolai N|NN|

Chronic inflammation
Granulocytic MDSC
Light-at-night-induced stress
Monocytic MDSC


Natural Infection of Tomatoes (Solanum lycopersicum) by Euphorbia yellow mosaic virus Isolates across Four Brazilian States.

Abstract: Severe yield losses induced by a complex of whitefly-transmitted Begomovirus species (family Geminiviridae) have been reported in tomatoes in Brazil (Reis et al. 2020). Nine isolates were obtained from tomato plants exhibiting begomovirus-like symptoms (viz. apical and interveinal chlorosis, yellow spots, and stunting) during independent field surveys: one isolate in Sumaré, São Paulo-SP State (isolate SP-066) in 2001, two in Serra Negra, Minas Gerais-MG (MG-012 and MG-016) in 2002, five in Caxias do Sul, Rio Grande do Sul-RS (RS-039, RS-045, RS-046, RS-047 and RS-058) in 2011 and one in Domingos Martins, Espírito Santo-ES (ES-148) in 2016. Disease incidence across all sampled fields ranged from 30% (in Domingos Martins-ES) to 90% in Sumaré-SP. Total DNA extraction was done by a modified CTAB method (Boiteux et al., 1999). Begomovirus infection was confirmed in all isolates by selective amplification of viral DNA-A segments using the primer pairs 'PAL1v1978 / PAR1c496' (Rojas et al., 1993) and 'BegomoAFor1' / 'BegomoARev1' (Ha et al., 2006), which produce two large and non-overlapping segments (≈1120 bp and ≈1205 bp, respectively). These PCR amplicons were initially characterized via direct Sanger dideoxy sequencing at CNPH. BLASTn analysis of the partial DNA-A genomes of these nine isolates indicated identity levels of 95-97% to three euphorbia yellow mosaic virus (EuYMV) reference isolates (= KY559532, JF756674, and KY559583) found infecting the weed Euphorbia heterophylla L. The entire DNA-A (2,609 nts = MN746971) and DNA-B (2,579 nts = MN746970) components of the MG-016 isolate were obtained via high-performance sequencing using Illumina HiSeq 2500 system (Macrogen Inc., South Korea). Sequences were assembled with the CLC Genomics Workbench program 10. Contigs were validated by BLASTx and BLASTn and compared to the ssDNA virus database at NCBI (www.ncbi.nlm.nih.gov). The fully-characterized MG-016 isolate displayed identity levels ranging from 97 to 99% to the EuYMV reference isolates as well as similar genomic features such as the conserved TATA box, nonanucleotide, and iterons (that were in agreement with a cognate nature of the DNA-A and DNA-B components). A partial sequence of the DNA-B genome was also obtained for the MG-012 isolate (MT7831942). The isolates MG-012 and MG-016 were found in mixed infections with tomato severe rugose virus (ToSRV) and tomato golden vein virus (TGVV), respectively. In addition, the complete DNA-A genomes of ES-148 (MN746972) and SP-066 (MN782438) were also obtained via a combination of primer walking and Sanger dideoxy sequencing, displaying 96-98% identity to EuYMV isolates. To our knowledge, this is the first report of multiple and independent events of natural infection of tomatoes by EuYMV isolates. Our results confirm the natural host status of tomatoes to EuYMV isolates as indicated in previous infectivity assays using biolistic inoculation (Barreto et al., 2013). The weed E. heterophylla is widely disseminated and very often present within tomato fields due to its higher levels of tolerance to the major herbicide (metribuzin) employed in this crop. Therefore, this weed may act as a persistent reservoir of tomato-infecting EuYMV isolates, which may allow the selection of viral populations potentially more adapted to this vegetable crop.

Duarte|Macaria Ferreira|MF|
Pereira Carvalho|Rita de Cássia|RC|
Dos Reis|Luciane de Nazaré Almeida|LNA|
Rojas|Maria J|MJ|
Gilbertson|Robert|R|
Costa|Helcio|H|
Boiteux|Leonardo Silva|LS|
Fonseca|Maria Esther N|MEN|

Vegetables
Causal Agent
Crop Type
Etiology
Subject Areas
Viruses and viroids


Changes and Influential Factors of Chemotherapy Usage for Non-Small Cell Lung Cancer Patients in China: A Multicenter 10-Year (2005-2014) Retrospective Study.

Abstract:
Background
Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients.

Patients and Methods
The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors.

Results
A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets.

Conclusion
From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.

Xing|Pu-Yuan|PY| Wang|Shou-Zheng|SZ| Shi|Ju-Fang|JF| Wang|Le|L| Hui|Zhou-Guang|ZG| Ren|Jian-Song|JS|0000-0002-6445-0153 Liu|Shang-Mei|SM| Qiao|You-Lin|YL|0000-0001-6380-0871 Dai|Min|M| Li|Jun-Ling|JL|

chemotherapy
non-small cell lung cancer
epidemiology
adjuvant chemotherapy
neo-adjuvant chemotherapy


To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer.

Abstract:
PURPOSE
To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer.

METHODS
A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded.

RESULTS
A total of 3038 records were identified of which 487 were screened based on the full text. Ultimately, 37 studies were included for narrative analysis. Meta-analysis could not be performed due to the large heterogeneity in study and reporting designs. Out of 37 studies, 30 reported a 'mean dose threshold' that needs to be achieved in order to expect a response. This threshold appears to be higher for hepatocellular carcinoma (HCC, 100-250 Gy) than for colorectal cancer metastases (CRC, 40-60 Gy). Reported thresholds tend to be lower for resin microspheres than when glass microspheres are used.

CONCLUSION
Although the existing evidence demonstrates a dose-response relationship in SIRT for both primary liver tumours and liver metastases, many pieces of the puzzle are still missing, hampering the definition of standardized dose thresholds. Nonetheless, most current evidence points towards a target mean dose of 100-250 Gy for HCC and 40-60 Gy for CRC. The field would greatly benefit from a reporting standard and prospective studies designed to elucidate the dose-response relation in different tumour types.

Westlund Gotby|Lovisa E L|LEL|0000-0002-1059-6616

SIRT Dosimetry Holmium Radioembolization TARE Yttrium


Hyperkalemia-induced acute flaccid paralysis: a case report.

Abstract: Acute flaccid paralysis is a medical emergency that may be caused by primary neuro-muscular disorders, metabolic alterations, and iatrogenic effects. Severe hyperkalemia is also a potential cause, especially in elderly patients with impaired renal function. Early diagnosis is essential for appropriate management. Here, we report the case of a 78-year-old woman with hypertension and diabetes presenting to the emergency department because of pronounced asthenia, rapidly evolving in quadriparesis. Laboratory examinations showed severe hyperkalemia of 9.9 mmol/L, metabolic acidosis, kidney failure (creatinine 1.6 mg/dl), and hyperglycemia (501 mg/dl). The electrocardiography showed absent P-wave, widening QRS, and tall T-waves. The patient was immediately treated with medical therapy and a hemodialysis session, presenting a rapid resolution of electrocardiographic and neurological abnormalities. This case offers the opportunity to discuss the pathogenesis, the clinical presentation, and the management of hyperkalemia-induced acute flaccid paralysis.

D'Ercole|Martina|M| Cipriani|Leda|L| Picciotto|Daniela|D| Bianzina|Stefania|S| Russo|Elisa|E| Viazzi|Francesca|F| Esposito|Pasquale|P|

D020805:Central Nervous System Viral Diseases

acute flaccid paralysis
hyperkalemia
diabetes
hemodialysis