Abstract:
OBJECTIVE
This study aimed to explore the association of A kinase-interacting protein 1 (AKIP1) expression with clinicopathological characteristics and prognosis in gastric cancer patients.

METHODS
Data of 260 gastric cancer patients were retrospectively reviewed. AKIP1 expression in tumor tissue and non-cancerous tissue specimens was detected by immunohistochemistry and semi-quantitatively scored according to the staining intensity and density. Moreover, the clinicopathological features were retrieved, and disease-free survival (DFS) and overall survival (OS) were calculated.

RESULTS
A kinase-interacting protein 1 expression was increased in tumor tissues compared with non-cancerous tissues (P < .001). In terms of tumor features, tumor AKIP1 high expression correlated with elevated T stage (P < .001) and raised TNM stage (P = .042), while did not correlate with pathological grade (P > .999), tumor size (P = .060), N stage (P = .180), or tumor location (P > .999). Meanwhile, tumor AKIP1 was not associated with the non-tumor features either. Kaplan-Meier curves disclosed that AKIP1 high expression patients had shorter DFS (P = .004) and OS (P = .043) compared with AKIP1 low expression patients. Univariate Cox's regression showed that AKIP1 high expression correlated with shorter DFS (P = .005, hazard ratio [HR] = 1.635) and OS (P = .046, HR = 1.519), whereas multivariate Cox's regression displayed that AKIP1 did not independently predict worse DFS (P = .172, HR = 1.276) or shorter OS (P = .433, HR = 1.183).

CONCLUSION
A kinase-interacting protein 1 may serve as a potential biomarker for deteriorative tumor features and poor prognosis in gastric cancer patients.

A kinase-interacting protein 1
gastric cancer
clinicopathological characteristics
disease-free survival
overall survival


A scalable solution for isolating human multipotent clinical-grade neural stem cells from ES precursors.

Abstract:
BACKGROUND
A well-characterized method has not yet been established to reproducibly, efficiently, and safely isolate large numbers of clinical-grade multipotent human neural stem cells (hNSCs) from embryonic stem cells (hESCs). Consequently, the transplantation of neurogenic/gliogenic precursors into the CNS for the purpose of cell replacement or neuroprotection in humans with injury or disease has not achieved widespread testing and implementation.

METHODS
Here, we establish an approach for the in vitro isolation of a highly expandable population of hNSCs using the manual selection of neural precursors based on their colony morphology (CoMo-NSC). The purity and NSC properties of established and extensively expanded CoMo-NSC were validated by expression of NSC markers (flow cytometry, mRNA sequencing), lack of pluripotent markers and by their tumorigenic/differentiation profile after in vivo spinal grafting in three different animal models, including (i) immunodeficient rats, (ii) immunosuppressed ALS rats (SOD1G93A), or (iii) spinally injured immunosuppressed minipigs.

RESULTS
In vitro analysis of established CoMo-NSCs showed a consistent expression of NSC markers (Sox1, Sox2, Nestin, CD24) with lack of pluripotent markers (Nanog) and stable karyotype for more than 15 passages. Gene profiling and histology revealed that spinally grafted CoMo-NSCs differentiate into neurons, astrocytes, and oligodendrocytes over a 2-6-month period in vivo without forming neoplastic derivatives or abnormal structures. Moreover, transplanted CoMo-NSCs formed neurons with synaptic contacts and glia in a variety of host environments including immunodeficient rats, immunosuppressed ALS rats (SOD1G93A), or spinally injured minipigs, indicating these cells have favorable safety and differentiation characteristics.

CONCLUSIONS
These data demonstrate that manually selected CoMo-NSCs represent a safe and expandable NSC population which can effectively be used in prospective human clinical cell replacement trials for the treatment of a variety of neurodegenerative disorders, including ALS, stroke, spinal traumatic, or spinal ischemic injury.

Bohaciakova|Dasa|D|
Hruska-Plochan|Marian|M|
Tsunemoto|Rachel|R|
Gifford|Wesley D|WD|
Driscoll|Shawn P|SP|
Glenn|Thomas D|TD|
Wu|Stephanie|S|
Marsala|Silvia|S|
Navarro|Michael|M|
Tadokoro|Takahiro|T|
Juhas|Stefan|S|
Juhasova|Jana|J|
Platoshyn|Oleksandr|O|
Piper|David|D|
Sheckler|Vickie|V|
Ditsworth|Dara|D|
Pfaff|Samuel L|SL|
Marsala|Martin|M|

D002460:Cell Line
D005434:Flow Cytometry
D006801:Humans
D039902:Multipotent Stem Cells
D058953:Neural Stem Cells

Amyotrophic lateral sclerosis (ALS)
Bioinformatic tools to study xenografts
Human embryonic stem cell (hESC)
Neural stem cell (NSC)
Spinal cord
Spinal traumatic injury


Health and economic benefits of public financing of epilepsy treatment in India: An agent-based simulation model.

Abstract:
OBJECTIVE
An estimated 6-10 million people in India live with active epilepsy, and less than half are treated. We analyze the health and economic benefits of three scenarios of publicly financed national epilepsy programs that provide: (1) first-line antiepilepsy drugs (AEDs), (2) first- and second-line AEDs, and (3) first- and second-line AEDs and surgery.

METHODS
We model the prevalence and distribution of epilepsy in India using IndiaSim, an agent-based, simulation model of the Indian population. Agents in the model are disease-free or in one of three disease states: untreated with seizures, treated with seizures, and treated without seizures. Outcome measures include the proportion of the population that has epilepsy and is untreated, disability-adjusted life years (DALYs) averted, and cost per DALY averted. Economic benefit measures estimated include out-of-pocket (OOP) expenditure averted and money-metric value of insurance.

RESULTS
All three scenarios represent a cost-effective use of resources and would avert 800,000-1 million DALYs per year in India relative to the current scenario. However, especially in poor regions and populations, scenario 1 (which publicly finances only first-line therapy) does not decrease the OOP expenditure or provide financial risk protection if we include care-seeking costs. The OOP expenditure averted increases from scenarios 1 through 3, and the money-metric value of insurance follows a similar trend between scenarios and typically decreases with wealth. In the first 10 years of scenarios 2 and 3, households avert on average over US$80 million per year in medical expenditure.

SIGNIFICANCE
Expanding and publicly financing epilepsy treatment in India averts substantial disease burden. A universal public finance policy that covers only first-line AEDs may not provide significant financial risk protection. Covering costs for both first- and second-line therapy and other medical costs alleviates the financial burden from epilepsy and is cost-effective across wealth quintiles and in all Indian states.

D017281:Cost of Illness
D003362:Cost-Benefit Analysis
D004827:Epilepsy
D005380:Financing, Government
D006801:Humans
D007194:India
D007342:Insurance Benefits
D013597:Systems Analysis
D016896:Treatment Outcome

Epilepsy
India
Cost-effectiveness
Universal public finance
Agent-based model


Impact of the severity of trauma on early retirement.

Abstract:
OBJECTIVE
To assess the association between Injury Severity Score (ISS) and subsequent risk of early retirement.

DESIGN
Observational cohort study with follow-up based on prospectively collected data. Hospital-based data were linked to national register data on pension reception and vital status.

SETTING
Level-one urban trauma centre.

PARTICIPANTS
Patients aged 18-64 years entering the trauma centre in Copenhagen during 1999-2007 who were alive after three days were followed until early retirement, death or emigration.

MAIN OUTCOME MEASURES
Primary outcome was early retirement, defined as receiving disability pension (unintentional) or voluntary early retirement pension (intentional) before the regular age of retirement (65 years). Relative risk of early retirement according to ISS (low, ISS 1-15 vs. high, ISS 16-75) was assessed using Cox proportional hazards regression, adjusted for age and gender.

RESULTS
Of all 6687 patients admitted to the trauma centre, a total of 1722 trauma patients were included and followed for a median of 6.2 years (interquartile range (IQR) 3.7-9.1). Of these, 1305 (75.8%) were males, median age was 35.0 years (IQR 25.4-46.5), and median ISS was 16 (IQR 9-25). Three hundred and twenty-two patients retired during follow-up. Patients with high ISS, compared to patients with low ISS, had an increased risk of early retirement, adjusted hazard ratio 2.60 (95% confidence interval (CI) 2.05-3.30; p<0.001). Relative increase in retirement risk was 1.04 (95% CI 1.03-1.05) per ISS point and 1.03 (95% CI 1.03-1.04) per year older. Gender was not found to be a significant risk factor (p=0.69). Five-year absolute risks of early retirement were 9.9% (95% CI 7.8-12.0%) for the low ISS group and 24.6% (95% CI 21.6-27.5%) for the high ISS group.

CONCLUSIONS
The risk of early retirement is 2.6 times higher in severely injured patients (ISS 16-75) than the risk in low to moderately injured patients (ISS 1-15) and they have a high absolute 5-year risk as well. Early, targeted interventions to assist with return to work might be able to reduce this risk.

Kuhlman|Michael Bilde|MB|
Lohse|Nicolai|N|
Sørensen|Anne Marie|AM|
Larsen|Claus Falck|CF|
Christensen|Karl Bang|KB|
Steinmetz|Jacob|J|

Trauma
Injury Severity Score
Cohort study
Early retirement pension


Multi-stage subunit vaccines against Mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost?

Abstract:
INTRODUCTION
More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections.

AREAS COVERED
Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants. The results revealed that multi-stage subunit vaccines induced a wide variety of immune-responses to all forms of TB, including CD8 + T-cell-mediated cytolytic and IFN-γ responses comparable to those induced by the BCG. They could potentially be used as a booster vaccine to improve the efficacy of the BCG.

EXPERT COMMENTARY
Multi-stage TB-vaccines could boost BCG-primed immunity, decrease bacterial loads and provide efficient protection against progressive TB-infection, especially in the latent phase. These types of vaccines administered before and after TB-infection can act as pre-exposure, post-exposure and even therapeutic vaccines. In the near future, these vaccines could provide a new generation of prime-vaccines or BCG prime-boosters.

Khademi|Farzad|F| Derakhshan|Mohammad|M| Yousefi-Avarvand|Arshid|A| Tafaghodi|Mohsen|M| Soleimanpour|Saman|S|

D000818:Animals
D000942:Antigens, Bacterial
D001500:BCG Vaccine
D006801:Humans
D007117:Immunization, Secondary
D055985:Latent Tuberculosis
D009169:Mycobacterium tuberculosis
D014376:Tuberculosis
D032581:Tuberculosis Vaccines
D022223:Vaccines, Subunit

Mycobacterium tuberculosis
BCG
Delivery systems/adjuvants
Multistage vaccines


Multidisciplinary approach in medicine: successful pregnancy in a patient with hyperinsulinism/hyperammonaemia (HI/HA) syndrome.

Abstract: This case illustrates the importance of multidisciplinary counselling and management of pregnancies in women with complex medical conditions, especially concerning women with cognitive impairment. We present a woman with hyperinsulinism/hyperammonaemia (HI/HA) syndrome. This syndrome is characterised by recurrent episodes of hypoglycaemia and elevated ammonia levels, which are potentially harmful to both the patient and a developing fetus. We describe a successful multidisciplinary approach during the pregnancy of a mentally challenged patient with HI/HA syndrome. This case illustrates the importance of personalised counselling during the preconception period and emphasises to include all disciplines involved in the medical and daily care of such a patient. In our case, the extensive multidisciplinary care during the preconception period, pregnancy, delivery and postpartum period resulted in a good maternal and neonatal outcome.

Benner|Bernadette J M|BJM|
Bazelmans|Mijke|M|
Huidekoper|Hidde|H|
Langeveld|Mirjam|M|
Langendonk|Janneke|J|
Schoenmakers|Sam|S|


Speech Recognition Outcomes in Adults With Slim Straight and Slim Modiolar Cochlear Implant Electrode Arrays.

Abstract:
OBJECTIVE
To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and slim lateral wall electrode (SLW) CI522 cochlear implant recipients.

STUDY DESIGN
Retrospective cohort study.

SETTING
Tertiary academic hospital.

METHODS
Comparison of postoperative AzBio sentence scores in quiet (percentage correct) in adult cochlear implant recipients with SME or SLW matched for preoperative AzBio sentence scores in quiet and aided and unaided pure tone average.

RESULTS
Patients with SLW (n = 52) and patients with SME (n = 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), mean preoperative aided pure tone average (55.9 [20.4] vs 58.1 [16.4] dB; P = .59), and mean AzBio score (percentage correct, 11.1% [13.3%] vs 8.0% [11.5%]; P = .25). At last follow-up (SLW vs SME, 9.0 [2.9] vs 9.9 [2.6] months), postoperative mean AzBio scores in quiet were not significantly different (percentage correct, 70.8% [21.3%] vs 65.6% [24.5%]; P = .29), and data log usage was similar (12.9 [4.0] vs 11.3 [4.1] hours; P = .07). In patients with preoperative AzBio <10% correct, the 6-month mean AzBio scores were significantly better with SLW than SME (percentage correct, 70.6% [22.9%] vs 53.9% [30.3%]; P = .02). The intraoperative tip rollover rate was 8% for SME and 0% for SLW.

CONCLUSIONS
Cochlear implantation with SLW and SME provides comparable improvement in audiologic functioning. SME does not exhibit superior speech recognition outcomes when compared with SLW.

MacPhail|Margaret E|ME|
Connell|Nathan T|NT|
Totten|Douglas J|DJ|
Gray|Mitchell T|MT|
Pisoni|David|D|
Yates|Charles W|CW|
Nelson|Rick F|RF|

speech recognition outcomes
slim straight
slim modiolar
cochlear implant
lateral wall
perimodiolar


Inadequate sleep and muscle strength: Implications for resistance training.

Abstract:
OBJECTIVES
Inadequate sleep (e.g., an insufficient duration of sleep per night) can reduce physical performance and has been linked to adverse metabolic health outcomes. Resistance exercise is an effective means to maintain and improve physical capacity and metabolic health, however, the outcomes for populations who may perform resistance exercise during periods of inadequate sleep are unknown. The primary aim of this systematic review was to evaluate the effect of sleep deprivation (i.e. no sleep) and sleep restriction (i.e. a reduced sleep duration) on resistance exercise performance. A secondary aim was to explore the effects on hormonal indicators or markers of muscle protein metabolism.

METHODS
A systematic search of five electronic databases was conducted with terms related to three combined concepts: inadequate sleep; resistance exercise; performance and physiological outcomes. Study quality and biases were assessed using the Effective Public Health Practice Project quality assessment tool.

RESULTS
Seventeen studies met the inclusion criteria and were rated as 'moderate' or 'weak' for global quality. Sleep deprivation had little effect on muscle strength during resistance exercise. In contrast, consecutive nights of sleep restriction could reduce the force output of multi-joint, but not single-joint movements. Results were conflicting regarding hormonal responses to resistance training.

CONCLUSION
Inadequate sleep impairs maximal muscle strength in compound movements when performed without specific interventions designed to increase motivation. Strategies to assist groups facing inadequate sleep to effectively perform resistance training may include supplementing their motivation by training in groups or ingesting caffeine; or training prior to prolonged periods of wakefulness.

Knowles|Olivia E|OE|
Drinkwater|Eric J|EJ|
Urwin|Charles S|CS|
Lamon|Séverine|S|
Aisbett|Brad|B|

D006801:Humans
D053580:Muscle Strength
D018482:Muscle, Skeletal
D055070:Resistance Training
D012890:Sleep
D012892:Sleep Deprivation

Performance
Resistance exercise
Sleep deprivation
Sleep restriction
Skeletal muscle health


Survey of Adverse Events After The First Dose of The ChAdOx1 nCoV-19 Vaccine: A Single-Center Experience in Korea.

Abstract: Vaccination is an important strategy for controlling the coronavirus disease 2019 (COVID-19) pandemic. We conducted a web-based cross-sectional survey based on Google Forms to collect data on adverse events (AEs) after the first dose of the ChAdOx1 nCoV-19 vaccine for healthcare workers (HCWs). Among the 1,676 vaccinated HCWs, 59.5% (998/1,676) responded to the survey. In total, 809 (81.1%) respondents reported experiencing AEs. There were no serious AEs, such as anaphylaxis. The most common AE was pain at the injection site (76.2%), followed by fatigue (75.9%), myalgia (74.9%), and fever (58.4%). HCWs in the younger age group experienced significantly more AEs than in the older age group.

Adverse event
Vaccine
Coronavirus disease
Surveillance


Management of combined massive burn and blast injury: A 20-year experience.

Abstract:
INTRODUCTION
Blast injuries are complex types of physical trauma resulting from direct or indirect exposure to an explosion, which can be divided into four classes: primary, secondary, tertiary, and quaternary. Primary blast injury results in damage, principally, in gas-containing organs such as the lungs (blast lung injury, BLI). BLI is defined as radiological and clinical evidence of acute lung injury occurring within 12h of exposure to an explosion and not due to secondary or tertiary injury. BLI often combines with cutaneous thermal injury, a type of quaternary blast injury, either in terrorist bomb attacks or in civilian accidental explosions. This report summarizes our experience in the management of combined massive burn and BLI at a Shanghai Burn Center in China.

METHODS
A retrospective observational analysis of clinical data was performed for massive burn patients with or without BLI during a 20-year interval. Patient characteristics, causes of injury, clinical parameters, management, and outcomes were recorded and evaluated.

RESULTS
A total of 151 patients (120 males and 31 females) with severe burn injury (≥50% TBSA) treated at the Burn Center of Changhai Hospital in Shanghai between July 1997 and June 2017 were enrolled in this study. Their mean age was 38.6±17.8 (3-75) years. Among them, 28 patients had combined BLI and burn injury and 39 patients had no BLI or smoke inhalation injury (non-BLI-SII). No significant difference was observed in the burn area or full-thickness burn area between the two groups. The lowest PaO2/fraction of inspired oxygen (FiO2) ratio during the first 24h in BLI patients was significantly lower than that in non-BLI-SII patients. Exudative changes were observed by X-ray radiography in all BLI patients but not in non-BLI-SII patients within 6h after injury. A significantly higher proportion of colloids were used for fluid resuscitation in BLI patients than that in non-BLI-SII patients. A higher proportion and longer time of mechanical ventilation were needed for BLI patients than those for non-BLI-SII patients, and a higher proportion of patients received sedative agents in the BLI group than those in the non-BLI-SII group. The first escharectomy was performed relatively later in BLI patients than in non-BLI-SII patients because of more time taken by BLI patients to recover from lung injury. The length of ICU and hospital stay in BLI patients was significantly longer than that in non-BLI-SII patients. No significant difference in the overall mortality was detected between these two groups.

CONCLUSION
It is a formidable challenge for clinicians to diagnose and manage massive burn patients combined with BLI. A comprehensive treatment approach is strongly recommended, including fluid resuscitation, airway management, mechanical ventilation, and surgical treatment. Given the high mortality of massive burn patients combined with BLI even in a recognized burn center, more prospective studies are encouraged to assess more effective strategies for the treatment of such patients.

Zheng|Xing-Feng|XF| Zhu|Feng|F| Fang|He|H| Xu|Da-Yuan|DY| Xu|Long|L| Chen|Tian-Sheng|TS| Zheng|Yong-Jun|YJ| Xiao|Shi-Chu|SC| Xia|Zhao-Fan|ZF|

Management
Burn
Blast lung injury
Combined injury


Development of a Croatian version of the US Hospital Survey on Patient Safety Culture questionnaire: dimensionality and psychometric properties.

Abstract:
BACKGROUND
The Hospital Survey on Patient Safety Culture (HSOPSC), originally developed in the USA, is used worldwide to assess patient safety culture in hospitals. A limited number of studies have provided data on psychometric properties outside of the US healthcare system. Our aim was to determine if all 12 dimensions of the US HSOPSC were applicable, valid and reliable to Croatian healthcare workers.

METHODS
The study was conducted from September 2010 to April 2011. Questions were translated into Croatian and then translated back into English. The questionnaires (ie, the Croatian translation of the US HSOPSC) were distributed in unmarked envelopes along with a consent form to all the doctors and nurses in four Croatian hospitals. The responses were analysed using explorative factor analyses, reliability testing, and confirmatory factor analyses.

RESULTS
The study included 561 healthcare workers in four Croatian hospitals--a response rate of 32.69%. Our results are similar to the original US sample, but with some differences: 11 dimensions with acceptable reliability scores were identified by exploratory factor analysis compared with the original 12 in the US sample; five of 12 dimensions had a Cronbach's α higher than 0.7, suggesting a reasonable fit to the original US HSOPSC; the dimensions 'Staffing' and 'Organisational learning--continuous improvement' were found to have a Cronbach's α <0.6. The use of confirmatory factor analysis confirmed a good fit to the original US model.

CONCLUSIONS
Results show that the Croatian translation of the US HSOPSC is compatible in 11 of the original 12 dimensions. Results suggest that for the purposes of research in Croatia, the dimensions 'Staffing', 'Communication openness', and 'Organisational learning-continuous improvement' should be revised. For example, the use of question A7 ('We use more agency/temporary staff than is best for patient care') in the context of European healthcare systems should be adapted or removed for the Croatian version of the US HSOPSC questionnaire.

Brborović|Hana|H| Šklebar|Ivan|I| Brborović|Ognjen|O| Brumen|Vlatka|V| Mustajbegović|Jadranka|J|

D010561:Personnel Staffing and Scheduling

Occupational & Industrial Medicine
Statistics & Research Methods


Multi-Robot Coordination Analysis, Taxonomy, Challenges and Future Scope.

Abstract: Recently, Multi-Robot Systems (MRS) have attained considerable recognition because of their efficiency and applicability in different types of real-life applications. This paper provides a comprehensive research study on MRS coordination, starting with the basic terminology, categorization, application domains, and finally, give a summary and insights on the proposed coordination approaches for each application domain. We have done an extensive study on recent contributions in this research area in order to identify the strengths, limitations, and open research issues, and also highlighted the scope for future research. Further, we have examined a series of MRS state-of-the-art parameters that affect MRS coordination and, thus, the efficiency of MRS, like communication mechanism, planning strategy, control architecture, scalability, and decision-making. We have proposed a new taxonomy to classify various coordination approaches of MRS based on the six broad dimensions. We have also analyzed that how coordination can be achieved and improved in two fundamental problems, i.e., multi-robot motion planning, and task planning, and in various application domains of MRS such as exploration, object transport, target tracking, etc.

Coordination
Multi-robot system
Multi-robot motion planning
Cooperation
Exploration and mapping
Multi-robot task planning
Object transport and manipulation
Target observation


Variability in Wheelchair Propulsion: A New Window into an Old Problem.

Abstract: Manual wheelchair users are at great risk for the development of upper extremity injury and pain. Any loss of upper limb function due to pain adversely impacts the independence and mobility of manual wheelchair users. There is growing theoretical and empirical evidence that fluctuations in movement (i.e., motor variability) are related to musculoskeletal pain. This perspectives paper discusses a local review on several investigations examining the association between variability in wheelchair propulsion and shoulder pain in manual wheelchair users. The experimental data reviewed highlights that the variability of wheelchair propulsion is impacted by shoulder pain in manual wheelchair users. We maintain that inclusion of these metrics in future research on wheelchair propulsion and upper limb pain may yield novel data. Several promising avenues for future research based on this collective work are discussed.

Sosnoff|Jacob J|JJ|
Rice|Ian M|IM|
Hsiao-Wecksler|Elizabeth T|ET|
Hsu|Iris M K|IM|
Jayaraman|Chandrasekaran|C|
Moon|Yaejin|Y|

injuries
motor variability
complexity
kinematics
kinetics
wheelchair biomechanics


The History of Trachoma and Current Prevalence (Spotlight on Iran): A Review Article.

Abstract:
Background
Trachoma as a common cause of infectious blindness is caused by Chlamydia trachomatis. This study aimed to review the available data from variety of sources and provide an overview of the epidemiological situation of Trachoma in Iran focused on the past seventy five years.

Methods
A literature search of English and Farsi articles regarding trachoma in Iran from the electronic databases and paper documents was performed. Original articles, case reports and letters were included.

Results
By the early and mid-20th century, trachoma was widely endemic with the prevalence rate of more than 60% in Iran. Currently, trachoma prevalence is significantly lower than in the past and the elimination of trachoma is achievable in the near future. The decline in active disease is mainly attributed to improvement of socio-economic situation and personal and environmental hygiene rather than targeted interventions for epidemic control.

Conclusion
Elimination of trachoma in Iran is achievable. However, trachoma prevalence estimation is required to be interpreted with some caution. Uncertainty around these estimates is partly because of the mismatch between the presence of infection and clinical findings.

Trachoma
Prevalence
Iran
Chlamydia trachomatis


Optimization of microbial assisted phytoremediation of soils contaminated with pesticides.

Abstract: 580 microbial strains were isolated from the rhizosphere of the plants Cucurbita pepo L. and Xanthium strumarium grown on soil contaminated with dichlorodiphenyltrichloroethane (DDT) and its metabolites. During the cultivation, two bacterial strains were selected because of their ability to grow on media containing 0.5-5.0 mg L-1 of dichlorodiphenyldichloroethylene (DDE) as the sole carbon source. They were identified as Bacillus vallismortis and Bacillus aryabhattai. Both of these species were shown to have a high capacity for the utilization of DDE - more than 90% of which was consumed after 21 days of cultivation. Laboratory experiments were carried out then to assess the possibility of using these strains for the decontamination of organochlorine pesticides (OCPs) contaminated soils. Inoculation of C. pepo and X. strumarium with our isolates B. vallismortis and B. aryabhattai resulted in a reduction of the pollutant stress to the plants as shown by an increase both in aboveground and in root biomass. The microorganisms enhanced the uptake and phytostabilization potential of C. pepo and X. strumarium and can be applied for the treatment of DDE contaminated soils.

Nurzhanova|Asil|A| Mukasheva|Togzhan|T| Berzhanova|Ramza|R| Kalugin|Sergey|S| Omirbekova|Anel|A| Mikolasch|Annett|A|


Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease.

Abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Its pathological hallmarks are senile plaques (SPs), which contain extracellular deposits of amyloid β (Aβ) protein fibrils and dystrophic neurites (DNs), and neurofibrillary tangles (NFTs) containing hyperphosphorylated tau. Impairment of protein-degradation systems, including the ubiquitin-proteasome and the autophagy-lysosome systems, has been proposed as one of the causes of the accumulation of these aberrant proteins in AD brains. Tom1 (target of Myb1) was originally identified by the induction of its expression by the v-Myb oncogene and is a part of two major protein-degradation systems. The present study was conducted by immunohistochemical and immunofluorescent stainings to show that Tom1 was localized in DNs, perisomatic granules (PSGs), and NFTs in AD brains. Moreover, in DNs, Tom1 colocalized with ubiquitin, lysosomal proteins, and Tom1-related proteins (Tollip and myosin VI), which act in both protein-degradation systems via Tom1. These results indicate that Tom1 plays important roles in protein-degradation systems in AD pathogenesis.

Makioka|Kouki|K| Yamazaki|Tsuneo|T| Takatama|Masamitsu|M| Ikeda|Masaki|M| Murayama|Shigeo|S| Okamoto|Koichi|K| Ikeda|Yoshio|Y|

D047908:Intracellular Signaling Peptides and Proteins

D052119:Lysosomal-Associated Membrane Protein 2

Alzheimer's disease
Dystrophic neurites
Tom1 (target of Myb1)
Perisomatic granules
Ubiquitin
Tollip
Autophagy
Myosin IV


Coexistence of lupus nephritis and sickle cell trait, an electron microscopic assessment of renal glomerular damage: Case report of a rare association.

Abstract: Because of similarities of the musculoskeletal, central nervous system, and renal manifestations in both diseases, diagnosing systemic lupus erythematosus (SLE) in sickle cell disease (SCD) patients can be difficult to establish. Although Sickle Cell Trait (SCT) is still considered a benign form of SCD, its impact on kidney injury and other renal manifestations is well recognized in the literature. In this case report, we look at the challenges that develop when diagnosing patients with a concurrence of both diseases and the importance of early recognition and treatment of lupus nephritis in SCT patients. We present a case of a male patient with sickle-cell trait who was admitted to our hospital complaining of low grade fever and pancytopenia for investigations proven to be SLE. A renal biopsy on electron microscopy assessment with different staining modalities as well as immune fluorescence revealed mixed pathological changes. We emphasize the importance in considering the presence of a coexisting autoimmune disease in a patient with sickle hemoglobinopathies even in the milder forms like SCT which may display an atypical and/or multisystem presentation. Also, the impact of the two conditions on the renal pathological changes should be expected to be more damaging even at early onset of SLE flare, and hence, an urge to start with more intensified immunosuppressive medications.

Elficki|Yahya|Y|
Rawas|Atif|A|
Bossei|Asseil Ali|AA|
Bdawod|Areej|A|
Zabani|Reem|R|
Shams|Bayan|B|

Lupus nephritis
Sickle cell trait
Systemic lupus erythematosus
Aplastic anemia
Febrile neutropenia


Sequencing 5-Hydroxymethyluracil at Single-Base Resolution.

Abstract: 5-hydroxymethyluracil (5hmU) is formed through oxidation of thymine both enzymatically and non-enzymatically in various biological systems. Although 5hmU has been reported to affect biological processes such as protein-DNA interactions, the consequences of 5hmU formation in genomes have not been yet fully explored. Herein, we report a method to sequence 5hmU at single-base resolution. We employ chemical oxidation to transform 5hmU to 5-formyluracil (5fU), followed by the polymerase extension to induce T-to-C base changes owing to the inherent ability of 5fU to form 5fU:G base pairing. In combination with the Illumina next generation sequencing technology, we developed polymerase chain reaction (PCR) conditions to amplify the T-to-C base changes and demonstrate the method in three different synthetic oligonucleotide models as well as part of the genome of a 5hmU-rich eukaryotic pathogen. Our method has the potential capability to map 5hmU in genomic DNA and thus will contribute to promote the understanding of this modified base.


Reliable assessment of BRCA1 and BRCA2 germline variants by next-generation sequencing: a multicenter study.

Abstract:
BACKGROUND
BRCA1/2 gene mutation testing, based on next-generation sequencing (NGS), has been gradually applied in the clinic to serve as preventive early screening for predisposed individuals or to provide treatment options for patients with hereditary breast or ovarian cancers. Here, we evaluated the accuracy of NGS-based mutation detection in BRCA1/2 and the consistency in variant interpretation among clinical laboratories to find the possible reasons underlying inaccurate results and discrepant variant interpretation.

METHODS
Laboratories were asked to use their routine procedures to detect six mimetic DNA samples with different BRCA1/2 germline variants. The results of variant detection were required to be submitted via a web-based evaluation system and were automatically scored, according to predefined criteria. The variant interpretation report, including the detailed clinical evidence, was summarized and analyzed for reasons underlying inconsistent results.

RESULTS
Overall, only 55.2% (16/29) of laboratories, whose detection score was higher than 90 points, was found to be an acceptable detection capability level. 82.9% (29/35) of the errors were genotype errors. The variant classification results were generally consistent, and 77.8% (7/9) of the variants were given the consistent classification answer. Only two single nucleotide variants (SNVs) had a discrepant classification opinion across laboratories.

CONCLUSIONS
The BRCA1/2 variant detection performance should be further improved, especially in reporting the correct genome coordinates. Inconsistent variant classification may be a result of the different clinical pieces of evidence collected by the laboratories. However, discordant clinical evidence also appeared within the same classification results. Therefore, our study provided clear clinical evidence assessment strategies for BRCA1/2 variants, which was aimed at obtaining a consistent variant classification strategy for providing accurate clinical reports to the clinicians.

Germline variant
Next-generation sequencing
BRCA1/2
Variant interpretation


Extraction and characterization of ternary complexes between natural organic matter, cations, and oxyanions from a natural soil.

Abstract: Natural organic matter (NOM) can have a significant influence on the mobility and fate of inorganic oxyanions, such as arsenic and selenium, in the environment. There is evidence to suggest that interactions between NOM and these oxyanions are facilitated by bridging cations (primarily Fe3+) through the formation of ternary complexes. Building on previous work characterizing ternary complexes formed in the laboratory using purified NOM, this study describes the extraction and characterization of intact ternary complexes directly from a soil matrix. The complexes are stable to the basic extraction conditions (pH 12) and do not appear to change when the pH of the extract is adjusted back to neutral. The results suggest that ternary complexes between NOM, cations, and inorganic oxyanions exist in natural soils and could play a role in the speciation of inorganic oxyanions in environmental matrices.

Peel|Hannah R|HR|
Martin|David P|DP|
Bednar|Anthony J|AJ|

Ternary complexes
Natural organic matter
Arsenic
Selenium
SEC-ICP-MS


Pharmacologic application of native GnRH in the winter anovulatory mare, II: accelerating the timing of pregnancy.

Abstract: Onset of the winter anovulatory period in mares is associated with a marked diminution in adenohypophyseal synthesis and release of LH. Native GnRH, unlike its synthetic agonists, stimulates the synthesis and secretion of LH in mares without pituitary refractoriness. Herein we tested the hypotheses that (1) the average Julian day of pregnancy can be accelerated by up to 2 months in winter anovulatory mares treated continuously with native GnRH beginning on February 1 and (2) mares will sustain luteal function and pregnancy after treatment withdrawal. Forty-two winter anovulatory mares were stratified by age, body condition score, and size of the largest follicle across two locations in a randomized design and assigned to one of three groups (n = 14 per group): (1) CONTROL: untreated, (2) GnRH-14: GnRH delivered subcutaneously in saline at a rate of 100 μg/h for 8 weeks (February 1-March 29) using four consecutive 14-day pumps (Alzet 2ML2), or (3) GnRH-28: GnRH delivered as in (2), but using two 28-day pumps (Alzet 2ML4). On development of a 35-mm follicle and expression of estrus, mares were bred the following day and treated with hCG. Pregnancies were confirmed using transrectal ultrasonography on Days 14, 24, 33, and 45, with blood samples collected to assess luteal function. Mares treated with GnRH (GnRH-14 and GnRH-28) did not differ reproductively in their responses and data were pooled for statistical comparisons. Mares treated with GnRH exhibited marked increases (P ≤ 0.04) in the frequency of development of a 35-mm follicle, submission rate for live cover and/or artificial insemination, ovulation, and pregnancy compared with control mares on treatment Day 56 (March 29). Interval to the first 35-mm follicle was 51.8 ± 4.9 and 19.3 ± 3.5 days (least square mean ± standard error of the mean) for control and GnRH-treated mares, respectively. Interval to pregnancy was 65.3 ± 6.7 and 28.6 ± 4.8 days (least square mean ± standard error of the mean) for control and GnRH-treated mares, respectively, excluding one GnRH-14 mare that failed to become pregnant over four cycles. By the end of the treatment period (March 29), only 21% of control mares were pregnant compared with 79% of GnRH-treated mares. Furthermore, mean serum concentrations of progesterone were similar to (GnRH-28; P = 0.26) or greater than (GnRH-14; P = 0.01) that of control mares from Day 0 to 46 postbreeding. Data illustrate that continuous administration of native GnRH is a highly efficient option for managing seasonal anovulation in mares and could be effectively used in the breeding industry if a user-friendly delivery option were available.

Thorson|J F|JF|
Prezotto|L D|LD|
Cardoso|R C|RC|
Allen|C C|CC|
Alves|B R C|BR|
Amstalden|M|M|
Williams|G L|GL|

GnRH Anovulatory Mare Pregnancy Seasonality


Prospects of Neutralizing Nanobodies Against SARS-CoV-2.

Abstract: Since December 2019, the SARS-CoV-2 has erupted on a large scale worldwide and spread rapidly. Passive immunization of antibody-related molecules provides opportunities for prevention and treatment of high-risk patients and children. Nanobodies (Nbs) have many strong physical and chemical properties. They can be atomized, administered by inhalation, and can be directly applied to the infected site, with fast onset, high local drug concentration/high bioavailability, and high patient compliance (no needles). It has very attractive potential in the treatment of respiratory viruses. Rapid and low-cost development of Nbs targeting SARS-CoV-2 can quickly be achieved. Nbs against SARS-CoV-2 mutant strains also can be utilized quickly to prevent the virus from escaping. It provides important technical supports for the treatment of the SARS-CoV-2 and has the potential to become an essential medicine in the toolbox against the SARS-CoV-2.

neutralizing
SARS-CoV-2
nanobodies (VHH)
phage display
receptor binding domain


Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics.

Abstract: A sudden transition in a system from an inanimate state to the living state-defined on the basis of present day living organisms-would constitute a highly unlikely event hardly predictable from physical laws. From this uncontroversial idea, a self-consistent representation of the origin of life process is built up, which is based on the possibility of a series of intermediate stages. This approach requires a particular kind of stability for these stages-dynamic kinetic stability (DKS)-which is not usually observed in regular chemistry, and which is reflected in the persistence of entities capable of self-reproduction. The necessary connection of this kinetic behaviour with far-from-equilibrium thermodynamic conditions is emphasized and this leads to an evolutionary view for the origin of life in which multiplying entities must be associated with the dissipation of free energy. Any kind of entity involved in this process has to pay the energetic cost of irreversibility, but, by doing so, the contingent emergence of new functions is made feasible. The consequences of these views on the studies of processes by which life can emerge are inferred.

Pascal|Robert|R|
Pross|Addy|A|
Sutherland|John D|JD|

D005075:Biological Evolution
D019143:Evolution, Molecular
D007700:Kinetics
D008958:Models, Molecular
D000069497:Origin of Life
D013816:Thermodynamics

origin of life
irreversibility
abiogenesis
dynamic kinetic stability
metabolism
systems chemistry


Comparison Between Carbapenems and β-Lactam/β-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.

Abstract:
BACKGROUND
Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development.

METHODS
We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs).

RESULTS
Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83-1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25-1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491-2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems.

CONCLUSIONS
These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

Muhammed|Maged|M|
Flokas|Myrto Eleni|ME|
Detsis|Marios|M|
Alevizakos|Michail|M|
Mylonakis|Eleftherios|E|


Imaging of facet joint diseases.

Abstract: Facet joints are the important articular pillars of the spine. Several pathologies can occur in and around the facet joint, including extra ossicles, traumatic dislocation, osteoarthritis, synovial cyst, axial spondyloarthritis, rheumatoid arthritis, calcium pyrophosphate deposition disease, septic arthritis, and malignant and benign neoplasms. Imaging is the mainstay to detect and characterize these diseases. In this review, we discuss the anatomy and function of facet joints, imaging techniques, and the imaging findings of several facet joint diseases. This information may be helpful to radiologists to make the correct diagnosis and optimize the management of patients with facet joint diseases.

D001172:Arthritis, Rheumatoid
D006801:Humans
D008159:Lumbar Vertebrae
D008279:Magnetic Resonance Imaging
D013581:Synovial Cyst
D021801:Zygapophyseal Joint

Disease
Pathology
Diagnosis
Magnetic resonance imaging
Tomography
Zygapophyseal joint


PAX5 haploinsufficiency induce cancer cell dormancy in Raji cells.

Abstract: PAX5 mutations have important role in leukemogenesis and leukemia relapse, cancer cell dormancy participates in cancer relapse, but there was no report about PAX5 mutation inducing cancer cell dormancy. we constructed the PAX5 deletion Raji cell lines using gene editing technology, evaluated dormancy biological characteristics of cell lines. Our results showed PAX5 haploinsufficiency restrained the proliferation of Raji cells, induced G0/G1 arrest of Raji cells, reduced chemotherapy sensitivity. The tumor formation rate reduced in PAX5 mutation Raji cells. Our results showed PAX5 insufficiency induced cancer cell dormancy in Raji cell.

Liang|Xue|X| Gu|Jia|J| Li|TongJuan|T| Zhao|Lei|L| Fu|Xing|X| Zhang|Wei|W| Wang|Jue|J| Shang|Zhen|Z| Huang|Wei|W| Zhou|Jianfeng|J|

PAX5
Haploinsufficiency
Cancer cell dormancy


Integrating Spatial Transcriptomics and Single-Cell RNA-seq Reveals the Gene Expression Profling of the Human Embryonic Liver.

Abstract: The liver is one of vital organs of the human body, and it plays an important role in the metabolism and detoxification. Moreover, fetal liver is one of the hematopoietic places during ontogeny. Understanding how this complex organ develops during embryogenesis will yield insights into how functional liver replacement tissue can be engineered and how liver regeneration can be promoted. Here, we combine the advantages of single-cell RNA sequencing and Spatial Transcriptomics (ST) technology for unbiased analysis of fetal livers over developmental time from 8 post-conception weeks (PCW) and 17 PCW in humans. We systematically identified nine cell types, and defined the developmental pathways of the major cell types. The results showed that human fetal livers experienced blood rapid growth and immigration during the period studied in our experiments, and identified the differentially expressed genes, and metabolic changes in the developmental process of erythroid cells. In addition, we focus on the expression of liver disease related genes, and found that 17 genes published and linked to liver disease mainly expressed in megakaryocyte and endothelial, hardly expressed in any other cell types. Together, our findings provide a comprehensive and clear understanding of the differentiation processes of all main cell types in the human fetal livers, which may provide reference data and information for liver disease treatment and liver regeneration.

Hou|Xianliang|X| Yang|Yane|Y| Li|Ping|P| Zeng|Zhipeng|Z| Hu|Wenlong|W| Zhe|Ruilian|R| Liu|Xinqiong|X| Tang|Donge|D| Ou|Minglin|M| Dai|Yong|Y|

spatial transcriptomics
fetal liver
single-cell RNA sequencing
erythrocyte
hepatoblast
multimodal intersection analysis


Emergency thoracic aortic stent grafting for acute complicated type B aortic dissection after a previous abdominal endovascular aneurysm repair.

Abstract: We report a case of acute type B aortic dissection with the complication of bowel ischemia and abdominal stent graft compression treated by emergency thoracic aortic stent grafting after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). A 69-year-old male was admitted to our hospital for sudden thoraco-abdominal pain. He had past treatment history of EVAR for AAA half a year ago. A computed tomography (CT) showed acute type B aortic dissection, and conservative treatment was initially performed. Three days after occurrence of aortic dissection, worsened abdominal pain and melena were observed. CT showed that the true lumen and abdominal stent graft was compressed by the false lumen. Emergency thoracic endovascular repair (TEVAR) was performed to close the entry tear. After the operation, the image views and the symptoms were improved. The state was still stable 6 months later. TEVAR for acute type B aortic dissection can become one of the effective treatments.

Yoshiga|Ryosuke|R| Morisaki|Koichi|K| Matsubara|Yutaka|Y| Yoshiya|Keiji|K| Inoue|Kentaro|K| Matsuda|Daisuke|D| Aoyagi|Yukihiko|Y| Tanaka|Shinichi|S| Okadome|Jun|J| Matsumoto|Takuya|T| Maehara|Yoshihiko|Y|


Adaptive Neural Networks Decentralized FTC Design for Nonstrict-Feedback Nonlinear Interconnected Large-Scale Systems Against Actuator Faults.

Abstract: The problem of active fault-tolerant control (FTC) is investigated for the large-scale nonlinear systems in nonstrict-feedback form. The nonstrict-feedback nonlinear systems considered in this paper consist of unstructured uncertainties, unmeasured states, unknown interconnected terms, and actuator faults (e.g., bias fault and gain fault). A state observer is designed to solve the unmeasurable state problem. Neural networks (NNs) are used to identify the unknown lumped nonlinear functions so that the problems of unstructured uncertainties and unknown interconnected terms can be solved. By combining the adaptive backstepping design principle with the combination Nussbaum gain function property, a novel NN adaptive output-feedback FTC approach is developed. The proposed FTC controller can guarantee that all signals in all subsystems are bounded, and the tracking errors for each subsystem converge to a small neighborhood of zero. Finally, numerical results of practical examples are presented to further demonstrate the effectiveness of the proposed control strategy.The problem of active fault-tolerant control (FTC) is investigated for the large-scale nonlinear systems in nonstrict-feedback form. The nonstrict-feedback nonlinear systems considered in this paper consist of unstructured uncertainties, unmeasured states, unknown interconnected terms, and actuator faults (e.g., bias fault and gain fault). A state observer is designed to solve the unmeasurable state problem. Neural networks (NNs) are used to identify the unknown lumped nonlinear functions so that the problems of unstructured uncertainties and unknown interconnected terms can be solved. By combining the adaptive backstepping design principle with the combination Nussbaum gain function property, a novel NN adaptive output-feedback FTC approach is developed. The proposed FTC controller can guarantee that all signals in all subsystems are bounded, and the tracking errors for each subsystem converge to a small neighborhood of zero. Finally, numerical results of practical examples are presented to further demonstrate the effectiveness of the proposed control strategy.

Actuators
Nonlinear systems
Backstepping
Adaptive systems
Artificial neural networks


Collapsing glomerulopathy and hemolytic uremic syndrome associated with falciparum malaria: completely reversible acute kidney injury.

Abstract: Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. Herein, we report a case of spontaneous resolution of AKI due to collapsing glomerulopathy (CG) and hemolytic-uremic syndrome (HUS) associated with P. falciparum malaria. Our case report highlights the fact that early intervention on the triggering cause of CG without a long course of steroids may obtain a remission of this severe subset of CG and may obtain a remission of HUS without therapeutic plasmapheresis The etiologic treatment of CG and HUS may avoid progression to end-stage renal disease.

Kute|Vivek Balkrishna|VB|
Trivedi|Hargovind L|HL|
Vanikar|Aruna V|AV|
Shah|Pankaj R|PR|
Gumber|Manoj R|MR|
Kanodia|Kamal V|KV|

Collapsing glomerulopathy
Acute kidney injury
Hemolytic-uremic syndrome
Plasmodium falciparum


Anti-inflammatory effects and enhancing immune response of freshwater hybrid catfish oil in RAW264.7 cells.

Abstract: The present study assessed the effect of freshwater hybrid catfish oil (FFO) on the inflammatory status of lipopolysaccharide (LPS)-stimulated RAW264.7 cells and investigated the underlying mechanisms. RAW264.7 cells were supplemented with various concentrations [0.125-2% in 0.5% propylene glycol (v/v)] of FFO with or without LPS (1 µg/ml) for 24 h. Inflammatory cytokines and mediators were quantified using ELISA and reverse transcription-quantitative PCR. The results revealed that FFO treatment inhibited the secretion and mRNA expression of the pro-inflammatory cytokines IL-6, IL-1β, TNF-α. In line with this, FFO suppressed the expression and secretion of the inflammatory mediators cyclooxygenase-2 and prostaglandin E2. FFO also reduced apoptotic body formation and DNA damage. Correspondingly, FFO enhanced the immune response by modulating the cell cycle regulators p53, cyclin D2 and cyclin E2. Accordingly, FFO may be developed as a nutraceutical product to prevent inflammation.

Tongmee|Bussarin|B| Ontawong|Atcharaporn|A| Lailerd|Narissara|N| Mengamphan|Kriangsak|K| Amornlerdpisan|Doungporn|D|

anti-inflammatory
immune response
freshwater hybrid catfish oil
cytokine
DNA damage


Development and matching of binocular orientation preference in mouse V1.

Abstract: Eye-specific thalamic inputs converge in the primary visual cortex (V1) and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalamo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels.

critical period for orientation matching


The Gender Violence - Implicit Association Test to measure attitudes toward intimate partner violence against women.

Abstract: Attitudes play a central role in intimate partner violence against women and are related to its origin, to the responses of women who suffer violence, and to the settings where it occurs. In fact, these attitudes are recognized as one of the risk factors linked to violent perpetration and to public, professional, and victim responses to this type of violence. However, even though available research generally shows a broad rejection of this violence, it remains a serious social and health problem that has reached epidemic proportions. This suggests that the information available about these attitudes (obtained through explicit and direct measures, i.e., self-reports) may be distorted or influenced by factors such as social desirability. In this context, the overall objective of our research project is to provide multi-method measures (explicit and implicit) of attitudes toward intimate partner violence against women, and the main goal of this paper is to propose an instrument for the implicit measurement of these attitudes. In this regard, the Implicit Association Test (IAT) is the most common procedure used, providing a superior predictive validity compared to explicit measures for socially sensitive topics. We will present an exploratory study that describes its adaptation for our purposes, and the development of the Gender Violence - Implicit Association Test (GV-IAT) to use among Spanish-speaking populations, and discuss the strengths and limitations of this proposal.


Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: comparison of SARS-CoV-2 with non-segmented RNA viruses.

Abstract: The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing global health crises. Children can be infected, but are less likely to develop severe neurological abnormalities compared with adults. However, whether SARS-CoV-2 can directly cause neurological impairments in pediatric patients is not known. The possible evolutionary and molecular relationship between SARS-CoV-2 and non-segmented RNA viruses were examined with reference to neurological disorders in pediatric patients. SARS-CoV-2 shares similar functional domains with neuroinvasive and neurotropic RNA viruses. The Spike 1 (S1) receptor binding domain and the cleavage sites at S1/S2 boundary are less conserved compared with the S2 among coronaviruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Neuroinvasive and neurotrophic non-segmented RNA viruses


Student perception about efficacy of preclinical fixed prosthodontic training to facilitate smooth transition to clinical context.

Abstract:
BACKGROUND
Studies indicate that the initial transition period between preclinical and clinical phases are the most stressful. The students have experienced the difficulty in performing clinical procedures due to the vast difference in the clinical and preclinical setup. It is better to identify the particular skill found poorly correlated, enabling educators to address the concerns. We sought the opinion and suggestion from the beneficiary student on fixed prosthodontics steps difficult to practice in clinical setup at the initial stage, their suggestion to overcome these shortcomings was also sought.

AIMS
To determine the fixed prosthodontics skills difficult to perform in a transition period due to poor correlation between preclinical and clinical training from our focus group study on the student's perception, and their suggestion regarding alternative methods to improve the preclinical training.

MATERIALS AND METHODS
Focus groups in the study were the students involved in clinical practice of fixed partial denture procedure. A well-constructed Questionnaire, designed to evaluate the difficult clinical steps in a transitional period and suggestion to improve the existing preclinical training was distributed to all focus group students. The response to the questionnaire was based on the five-point Likert scale.

STATISTICAL ANALYSIS USED
Medians, frequencies were used to assess their perception on preclinical training and suggestion.

RESULTS
A total of 97 students participated in the study, 88% response received during the survey. The clinical steps student felt difficult during a transition period from preclinical to clinical phase were positional variations of teeth (52.6%-63.9%), fluid control (48.5-67.1%), shade selection procedure (29.9%-50.5%), subgingival cervical finish line preparation (38.1-51.5%), and gingival retraction procedure. The students felt that the inclusion of problem-based learning, preclinical patient exposure, and better simulation will alleviate the stress during the transition period.

CONCLUSIONS
This study highlighted the tooth preparation steps found difficult to practice in a transition period between preclinical and clinical phases. This study also obtained suggestions from the students for innovative upgradation of the course curricula.

Haralur|Satheesh B|SB|
Al-Malki|Abdullah Edrees|AE|

transition period
preclinical training
Fixed partial denture


Partial loudness at masker onset indicates temporal effects at supra-threshold levels.

Abstract: This study examines temporal effects both at threshold and at supra-threshold levels. The level needed to detect a short-duration 4.0-kHz signal was measured for signals presented with different onset delays relative to a 300-ms broadband noise masker: 100 ms and 5 ms before the onset of the masker and 5 ms and 100 ms after the onset of the masker. Loudness matches between the signal in quiet and the signal at the same four onset delays were obtained for five presentation levels of the short-duration signal and for three masker levels. The temporal effect was defined as the level difference between the signals near masker onset and the signals well before or well after masker onset, needed to reach threshold and/or achieve equal loudness. Both at threshold and at supra-threshold levels temporal effects were observed consistent with a decrease in gain at the masker frequency during the course of the masker. The temporal effect was not restricted to simultaneous masking, but was also found for backward masking. In both cases the temporal effects were stronger at supra-threshold levels than at threshold. This may be caused by a transient effect at masker onset. The almost simultaneous onset of the signal and the masker makes it difficult for subjects to separate signal from the masker, especially when the signal level is close to masked threshold.

van Beurden|Maarten F B|MFB|
Dreschler|Wouter A|WA|

D000161:Acoustic Stimulation
D001309:Auditory Threshold
D006801:Humans
D008144:Loudness Perception
D009622:Noise
D010470:Perceptual Masking
D011571:Psychoacoustics
D017603:Signal Detection, Psychological
D013997:Time Factors

Simultaneous masking
Auditory threshold
Loudness perception
Overshoot
Psychoacoustics


Molecular Insights into the Copper-Sensitive Operon Repressor in Acidithiobacillus caldus.

Abstract: The copper-sensitive operon repressor (CsoR) family, which is the main Cu(I)-sensing family, is widely distributed and regulates regulons involved in detoxification in response to extreme copper stress (a general range of ≥3 g/liter copper ions). Here, we identified CsoR in hyper-copper-resistant Acidithiobacillus caldus (CsoRAc), an organism used in the bioleaching process of copper ores. CsoRAc possesses highly conserved Cu(I) ligands and structures within the CsoR family members. Transcriptional analysis assays indicated that the promoter (PIII) of csoR was active but weakly responsive to copper in Escherichia coli. Copper titration assays gave a stoichiometry of 0.8 mol Cu(I) per apo-CsoRAc monomer in vitro combined with atomic absorption spectroscopy analysis. CuI-CsoRAc and apo-CsoRAc share essentially identical secondary structures and assembly states, as demonstrated by circular dichroism spectra and size exclusion chromatography profiles. The average dissociation constants (K = 2.26 × 10-18 M and 0.53 × 10-15 M) and Cu(I) binding affinity of apo-CsoRAc were estimated by bathocuproine disulfonate (BCS) and bicinchoninic acid (BCA) competition assays, respectively. Site-directed mutations of conserved Cu(I) ligands in CsoRAc did not significantly alter the secondary structure or assembly state. Competition assays showed that mutants had the same order of magnitude of Cu(I) binding affinity as apo-CsoRAc. Moreover, apo-CsoRAc could bind to the DNA fragment P08430 in vitro, although with low affinity. Finally, a working model was developed to illustrate putative copper resistance mechanisms in A. caldus. IMPORTANCE Research on copper resistance among various species has attracted considerable interest. However, due to the lack of effective and reproducible genetic tools, few studies regarding copper resistance have been reported for A. caldus. Here, we characterized a major Cu(I)-sensing family protein, CsoRAc, which binds Cu(I) with an attomolar affinity higher than that of the Cu(I)-specific chelator bathocuproine disulfonate. In particular, CsoR family proteins were identified only in A. caldus, rather than A. ferrooxidans and A. thiooxidans, which are both used for bioleaching. Meanwhile, A. caldus harbored more copper resistance determinants and a relatively full-scale regulatory system involved in copper homeostasis. These observations suggested that A. caldus may play an essential role in the application of engineered strains with higher copper resistance in the near future.

Hou|Shaoxiang|S| Tong|Yanjun|Y| Yang|Hailin|H| Feng|Shoushuai|S|

D015964:Gene Expression Regulation, Bacterial

copper-sensitive operon repressor
Acidithiobacillus
extreme copper stress
copper resistance determinants


Decontamination of rough implant surfaces colonized by multispecies oral biofilm by application of leukocyte- and platelet-rich fibrin.

Abstract:
BACKGROUND
Decontamination of biofilm-infected rough implant surfaces is challenging. Platelet rich blood products have been shown to have anti-microbial properties against periodontal pathogens. Our aim was to investigate the effect of a potential biological implant surface disinfectant, leukocyte- and platelet-rich fibrin (L-PRF), on a mature oral multispecies biofilm on a rough titanium surface.

METHODS
Sandblasted, large grit, acid-etched (SLA) titanium disks were inoculated with subgingival dental plaque and cultured anaerobically for 21 days. The L-PRF membranes were collected from 12 donors in three trials (four donors in each trial). The disks were rinsed with 0.9% NaCl and exposed to the cell-rich portion of the L-PRF membranes for 48 hours followed by scanning electron microscope (SEM) analysis immediately or after rinsing with 0.9% NaCl prior to fixation. The presence of platelet factor-4 in the rinse samples was analyzed by Western blotting. Remaining bacteria were quantified from SEM images of the implant surfaces and their numbers statistically compared.

RESULTS
The L-PRF-treated samples without rinsing displayed numerous cells with multiple pseudopodia in immediate contact with bacteria that appeared perforated and increased in size. The cells were identified as platelets based on morphological criteria and by positive reaction for platelet factor-4 by Western blotting. After post-treatment rinsing, the L-PRF-treated disks displayed a significant reduction in bacterial counts (in average 92% reduction).

CONCLUSION
Application of L-PRF significantly reduced bacterial counts on contaminated SLA titanium surface, most likely through anti-microbial action by platelets.

Schuldt|Luisa|L| Bi|Jiarui|J| Owen|Gethin|G| Shen|Ya|Y| Haapasalo|Markus|M| Häkkinen|Lari|L| Larjava|Hannu|H|

biofilm
platelet-rich fibrin
titanium
blood platelets
peri-implantitis


Prediction of IgG1 aggregation in solution.

Abstract: Interest in monoclonal antibody aggregation is increasing as aggregates of biopharmaceuticals can cause an immunogenic response when injected into the body. In this work, a stoichiometric reaction model from concentration-time data is developed to predict the dimer ratio in stored antibody solutions over time. IgG1 was incubated at pH from 4.5 to 5.5, salt concentrations from 100 to 600 mmol/kg and protein concentrations of 10.6-26.3 g/L; samples were taken at intervals of 20 min to 5 h over time periods from 4 h to 7.6 days, and analyzed with size-exclusion chromatography. The experiments showed the formation of dimers from monomers, but no higher order aggregates. Dilution of samples containing dimers led to the reversal of the dimerization reaction. Measurements of the concentrations of each component were made by fitting exponentially modified Gaussian peaks to the chromatograms used to measure the concentrations of the different forms of protein. This stoichiometric reaction model was able to predict the formation of dimers by the antibody studied. The equilibrium constant was found to be dependent on the salt concentration, and the kinetic constant showed a dependence on the pH of the solution. The prediction of the aggregation leads to a possibility of optimizing the conditions in order to prevent the dimer formation and to maximize the monomer concentration.

Ojala|Frida|F|
Degerman|Marcus|M|
Hansen|Thomas Budde|TB|
Broberg Hansen|Ernst|E|
Nilsson|Bernt|B|

Aggregation
Solution
Antibodies
Biopharmaceuticals
Reversible reaction model


Plasma Robot Engineering: The Next Generation of Precision Disease Management.

Abstract: Robotics, once combined with cold atmospheric plasma, represent key elements of the next generation of personalized medicine and contribute to the effective yet immediate response to pandemics. Plasma robots can serve as CAP delivery vehicle to assist in tumor therapeutics and viral disease prevention in addition to the already prevalent utilities of robots in precision surgery, diagnosis, and risk prevention. Plasma robots may develop at either the macro- or the micro- scale, successful navigations at which require joint effort from multiple research domains.

Cold atmospheric plasma
Therapeutics
Prevention
Diagnosis
COVID-19
Medical robot


Transcriptome profiling reveals response genes for downy mildew resistance in cucumber.

Abstract: We discovered a potential defense pathway of cucumber to downy mildew. The signaling that activates the pathways of ROS and lignin accumulation may play an important role in the defense response. Many resistance genes were identified by transcriptome analysis. Downy mildew (DM), caused by Pseudoperonospora cubensis, is one of the most destructive diseases and causes severe yield losses of cucumber. However, the genes and pathways involved in regulating DM resistance were still poorly understood. In our study, we observed that the highly sensitive inbred line 53 (IL53) exhibited more severe disease symptoms than the highly resistant inbred line 51 (IL51) under P. cubensis infection. Furthermore, lignin, limiting the germination and extension of P. cubensis, and H2O2, as a signaling molecule during the resistant process, were both shown to increase, indicating that the signaling that activates these pathways might be responsible for the resistance divergence between IL51 and IL53. Transcriptome analysis, using the resistant and susceptible pools in F2 populations with IL51 and IL53 as parents, showed that a series of differentially expressed genes was involved in multiple functions of defense response: pathogen-associated molecular pattern recognition, signal transduction, reactive oxygen species and lignin accumulation, and transcription regulators. Combining physiological data with transcriptomes, we predicted a potential molecular mechanism of cucumber resistance to DM. Our research provided a foundation for further studies on the mechanism of cucumber resistance to DM.

D018553:Cucumis sativus
D060467:Disease Resistance
D020869:Gene Expression Profiling
D006861:Hydrogen Peroxide
D044742:Peronospora
D010935:Plant Diseases
D059467:Transcriptome

Downy mildew
Cucumber
Lignin
Defense response
H2O2
Gene regulatory networks


Systematic Review and Meta-Analysis on Using Acupressure to Promote the Health of Older Adults.

Abstract: Acupressure is noninvasive, safe, and appropriate for use among older adults. However, there remains little evidence of the common elements that contribute to the effectiveness of acupressure in promoting the health of older adults. A systematic review using meta-analysis was designed to examine the effects of acupressure on the health promotion in older adults. Studies published between 2012 and 2017 were searched for in 11 electronic databases. Acupressure was highly effective for improving sleep quality and cognitive functioning (0.85, 95% confidence interval [CI] = [0.49, 1.22]; 1.23, 95% CI = [0.88, 1.59]). A slight to moderate effect was found in alleviating constipation (0.37, 95% CI = [0.03, 0.71]), and a moderate effect was found for alleviating pain and improving quality of life (0.71, 95% CI = [0.09, 1.32]; 0.59 95% CI = [0.36, 0.82]).

Chen|Meng-Chin|MC| Yang|Li-Yen|LY| Chen|Kuei-Min|KM|0000-0002-4075-9607 Hsu|Hui-Fen|HF|

systematic review
meta-analysis
acupressure
older adults
health promotion
aged


Antioxidant and anti-inflammatory activities of Aerva pseudotomentosa leaves.

Abstract:
CONTEXT
Aerva pseudotomentosa Blatt. & Hallb. (Amaranthaceae), commonly called "Bui";, is a medicinal plant of the arid region. It is used for the treatment of inflammatory disorders, such as rheumatic pain, and healing of wounds, which are associated with oxidative stress.

OBJECTIVE
The present study evaluated the antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its anti-inflammatory effect in rats.

MATERIAL AND METHODS
The aqueous extract (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and hydrogen peroxide free radical scavenging, reducing power, and anti-lipid peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and formalin-induced paw oedema models in rats. APAE (200 and 400 mg/kg) and standard drug, indomethacin (10 mg/kg), were administered orally 1 h before carrageenan/formalin administration and inflammation was noted up to 5 h.

RESULTS
HPLC analysis of APAE revealed the presence of rutin. APAE showed significant scavenging effect on DPPH (IC50 49.37 μ g/mL) and peroxide (IC50 288.2 μ g/mL) radicals. The extract exhibited reducing potential and inhibition of lipid peroxidation. APAE treatment significantly attenuated mean increase in paw volume and exhibited inhibition of paw oedema in both in vivo models with inhibition of 45.11% and 49.42%, respectively at 5 h.

DISCUSSION AND CONCLUSION
APAE exhibited <italic>in vitro</italic> antioxidant and anti-inflammatory activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant potential, due to the presence of rutin and other phenolics. This study substantiates folk use of leaves in inflammatory disorders.

Pandey|Abhishek|A|
Kaushik|Atul|A|
Wanjari|Manish|M|
Dey|Yadu Nandan|YN|
Jaiswal|Bhagat Singh|BS|
Dhodi|Anamika|A|

D002851:Chromatography, High Pressure Liquid

Bui
DPPH
Carrageenan
Rutin
Desert zone
Flavonoids


Potential Role of Endonuclease Inhibition and Other Targets in the Treatment of Influenza.

Abstract:
BACKGROUND
Influenza is a single-stranded RNA virus that is highly contagious and infects millions of people in the U.S. annually. Due to complications, approximately 959,000 people were hospitalized and another 79,400 people died during the 2017-2018 flu season. While the best methods of prevention continue to be vaccination and hygiene, antiviral treatments may help reduce symptoms for those who are infected. Until recently, the only antiviral drugs in use have been the neuraminidase inhibitors: oseltamivir, zanamivir, and peramivir.

OBJECTIVE
We reviewed novel drug targets that can be used in the treatment of influenza, particularly in the case of neuraminidase inhibitor-resistant strains that may emerge.

RESULTS
More recently, a drug with a new mechanism of action has been approved. Baloxavir marboxil inhibits the influenza cap-dependent endonuclease that is needed for the virus to initiate replication within the host cell. This endonuclease target is within the polymerase acid (PA) subunit of RNA polymerase. Since the RNA-dependent RNA polymerase consists of two other subunits, polymerase basic 1 and 2, RNA polymerase has several targets that prevent viral replication. Other targets still under investigation include viral kinases, endocytosis, and viral fusion.

CONCLUSION
Due to the possibility of viral mutations and resistance, it is important to have antivirals with different mechanisms available, especially in the case of a new pandemic strain. Several novel antivirals are within various stages of development and may represent new classes of treatments that can reduce symptoms and complications in those patients who may be at higher risk.

endonuclease Influenza antivirals neuraminidase polymerase pandemic hemagglutinin resistance.


A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming.

Abstract: Neurotransmitter release during synaptic transmission comprises a tightly orchestrated sequence of molecular events, and Munc13-1 is a cornerstone of the fusion machinery. A forward genetic screen for defects in neurotransmitter release in Caenorhabditis elegans identified a mutation in the Munc13-1 ortholog UNC-13 that eliminated its unique and deeply conserved C-terminal module (referred to as HC2M) containing a Ca2+-insensitive C2 domain flanked by membrane-binding helices. The HC2M module could be functionally replaced in vivo by protein domains that localize to synaptic vesicles but not to the plasma membrane. HC2M is broadly conserved in other Unc13 family members and is required for efficient synaptic vesicle priming. We propose that the HC2M domain evolved as a vesicle/endosome adaptor and acquired synaptic vesicle specificity in the Unc13ABC protein family.

D000595:Amino Acid Sequence
D000818:Animals
D017173:Caenorhabditis elegans
D029742:Caenorhabditis elegans Proteins
D005089:Exocytosis
D008565:Membrane Proteins
D009154:Mutation
D009419:Nerve Tissue Proteins
D018377:Neurotransmitter Agents
D000072417:Protein Domains
D017384:Sequence Deletion
D009435:Synaptic Transmission
D013572:Synaptic Vesicles


GROWTH, HUSBANDRY, AND DIETS OF FIVE SUCCESSFULLY HAND-REARED ORPHANED GIRAFFE CALVES (GIRAFFA CAMELOPARDALIS ROTHSCHILDI AND GIRAFFA CAMELOPARDALIS RETICULATA).

Abstract: Giraffe in the wild are in ongoing decline because of poaching and habitat loss and fragmentation, and were recently assessed as "vulnerable" on the IUCN (International Union for Conservation of Nature) Red List of Threatened Species. Captive breeding and saving each individual are therefore becoming more important to save this species from extinction. This paper describes the husbandry and diets of successfully hand-reared Rothschild's giraffes (Giraffa camelopardalis rothschildi; n = 3) and reticulated giraffes (Giraffa camelopardalis reticulata; n = 2). All calves were initially fed with bovine colostrum followed by cow's milk (Holstein milk; Holstein milk with 10% of bovine colostrum; Jersey and Guernsey milk). Additionally, lactase enzymes (Lactaidt, Johnson & Johnson Inc., Guelp, Ontario N1K1A5, Canada) and probiotics (Probiost, Vets Plus, Inc., Menomonie, WI 54751, USA) were used. Average growth varied from 764 to 1,239 g/day from birth until 2 mo of age and between 508 and 1,161 g/day from birth until last measurement before weaning. Hand-reared calves gained up to 21 cm in height within the first month and 82-138% of their birth weight during the first 2 mo. The giraffes were weaned at 6 (n = 1), 8 (n = 3), and 11.5 (n = 1) mo and successfully socialized and introduced to other giraffes. The described diets and husbandry proved to be effective in all five calves. Large amounts of cow's milk per feeding (up to 6 L) did not result in gastrointestinal problems.

Meuffels|Janine|J|
Ververs|Cyrillus|C|
Pootoolal|Jason|J|
Zijll Langhout|Martine van|MV|
Govaere|Jan|J|

hand-rearing
Giraffa
growth measurements
maternal rejection
nutrition


Substrate-decoupled, bulk-acoustic wave gyroscopes: Design and evaluation of next-generation environmentally robust devices.

Abstract: This paper reports on a new type of high-frequency mode-matched gyroscope with significantly reduced dependencies on environmental stimuli such as temperature, vibration, and shock. A novel stress-isolation system is used to effectively decouple an axis-symmetric bulk-acoustic wave (BAW) vibratory gyro from its substrate, minimizing the effect that external sources of error have on the offset and scale factor of the device. Substrate-decoupled (SD) BAW gyros with a resonance frequency of 4.3 MHz and Q values near 60 000 were implemented using the high aspect ratio poly and single-crystal silicon (HARPSS) process to achieve ultra-narrow capacitive gaps. Wafer-level packaged sensors were interfaced with a customized application-specific integrated circuit (ASIC) to achieve low variations in the offset across temperature (±26° s-1 from -40 to 85 °C), supreme random-vibration immunity (0.012° s-1 gRMS -1) and excellent shock rejection. With a scale factor of 800 μV (°s-1)-1, the SD-BAW gyro system attains a large full-scale range (±1250° s-1) with a non-linearity of less than 0.07%. A measured angle-random walk (ARW) of 0.39°/√h and a bias instability of 10.5°h-1 are dominated by the thermal and flicker noise of the integrated circuit (IC), respectively. Additional measurements using external electronics show bias-instability values as low as 3.5°h-1, which are limited by feed-through signals coupled from the drive loop to the sense channel, which can be further reduced through proper re-routing of the gyroscope pin-out configuration.

Serrano|Diego E|DE|
Zaman|Mohammad F|MF|
Rahafrooz|Amir|A|
Hrudey|Peter|P|
Lipka|Ron|R|
Younkin|Duane|D|
Nagpal|Shin|S|
Jafri|Ijaz|I|
Ayazi|Farrokh|F|

Bulk-acoustic wave
MEMS gyroscope
environmental stability
support loss
vibration rejection


Experience of fatigue, and its relationship to physical capacity and disease severity in men and women with COPD.

Abstract:
INTRODUCTION
Several differences have been reported in the clinical characteristics of chronic obstructive pulmonary disease (COPD) between men and women. Differences have been found in the association between respiratory symptoms and lung function, and in the factors associated with dyspnea. This raises the question of whether there are differences between the sexes in the relationship between fatigue, the second most prevalent symptom, and the variables of physical capacity and disease severity.

OBJECTIVES
To examine the experience of fatigue and its relationship to physical capacity and disease severity in men and women with COPD.

METHODS
In a cross-sectional study 121 patients with COPD (54 men and 67 women), the experience of fatigue (frequency, duration, and severity) and physical capacity (lung function, 6-minute walk distance [6MWD], grip strength, and timed-stand test) were assessed. Disease severity was graded according to the Body mass index, airway Obstruction, Dyspnoea and Exercise capacity (BODE) index. Two multiple logistic regression models were tested, both of which were performed separately in men and women, to examine the association between the experience of fatigue and variables of physical capacity and the BODE index.

RESULTS
Eighty-nine (73.6%) patients experienced fatigue, with similar proportions in men and women. The men with fatigue had worse physical capacity and more severe disease than did the men without fatigue: for men with and without fatigue, respectively, the percent of predicted forced expiratory volume in 1 second (FEV1) (mean [standard deviation]) was 47 (14) vs 64 (17); the 6MWD (mean [standard deviation]) was 398 (138) vs 539 (105) m; and the BODE index (median [quartile 1-3]) was 3 (2-5) vs 1 (0-1) (P<0.01). In women, only higher leg fatigue post-6MWD was seen among those experiencing fatigue compared with women without fatigue: for women with and without fatigue, respectively, leg fatigue (median [quartile 1-3]) was 4 (3-5) vs 2 (0-3) (P<0.001). The regression models showed that the 6MWD and the BODE index were associated with fatigue in both men and women, but in women, leg fatigue remained an independent associate in both models.

CONCLUSION
Exercise capacity and disease severity were associated with fatigue in both men and women. In women, leg fatigue was strongly associated with fatigue, which warrants further investigation.

Tödt|Kristina|K| Skargren|Elisabeth|E| Kentson|Magnus|M| Theander|Kersti|K| Jakobsson|Per|P| Unosson|Mitra|M|

D029424:Pulmonary Disease, Chronic Obstructive

chronic obstructive pulmonary disease
leg fatigue
disease state
functional capacity
sex differences
symptom experience


Malignant Pleural Mesothelioma, Biphasic Type: An Unusual and Insidious Case of Rapidly Progressive Small Blue Cell Tumor.

Abstract: Malignant pleural mesothelioma (MPM) is a rare neoplasm. It predominantly affects elderly individuals aged over 70 years presenting with a unilateral pleural tumor usually associated with previous asbestos exposure. The respiratory symptoms are associated with ipsilateral pleural involvement with concomitant pleural effusions. The diagnosis of MPM is established by the morphologic and immunohistochemical features of a cytologic specimen. MPM can present as three histologic subtypes: epithelioid, sarcomatoid, or biphasic. We present a case of an 85-year-old Caucasian female with a history of occupational asbestos exposure. She complained of 1-week history of progressive sharp right flank and scapular pain with mild shortness of breath, dry cough and pleuritic chest pain. CT of the chest showed a large loculated right pleural effusion with adjacent pleural thickening. CT abdomen and pelvis was negative for other neoplastic findings. CT-guided core biopsy of the right pleural-based mass was positive for a spindle to plasmacytoid small blue cell tumor. An extensive immunohistochemical panel was non-specific. A focal OSCAR keratin and WT-1 expression in the absence of carcinoma markers, a malignant mesothelioma, biphasic type was diagnosed. Further workup with PET-CT and cytotoxic chemotherapy combined with immunotherapy or tyrosine kinase inhibitors was recommended by oncology. The patient refused further imaging and treatment, and palliative care was consulted.

Salazar|Carlos|C|
Kanter Md|Nelson|N|
Abboud|Amer|A|


Second-Order Nonlinear Optical Properties of a Dithienylethene-Indolinooxazolidine Hybrid: A Joint Experimental and Theoretical Investigation.

Abstract: The nonlinear optical (NLO) properties of a double photochrome molecular switch are reported for the first time by considering the four trans forms of a dithienylethene-indolinooxazolidine hybrid. The four forms are characterized by means of hyper-Rayleigh scattering (HRS) experiments and quantum chemical calculations. Experimental measurements provide evidence that the pH- and light-triggered transformations between the different forms of the hybrid are accompanied by large variations of the first hyperpolarizability, which makes this compound an effective multistate NLO switch. Quantum chemical calculations conducted at the time-dependent Hartree-Fock and time-dependent DFT levels agree with the experimental data and allow a complete rationalization of the NLO responses of the different forms. The HRS signal of the forms with an open indolinooxazolidine moiety are more than one order of magnitude larger than that measured for the other forms, whereas the open/closed status of the dithienylethene subunit barely influences the dynamic NLO properties. However, extrapolation of the NLO responses to the static limit leads to univocally distinguishable intrinsic responses for three of the various forms. This hybrid system thus acts as a highly efficient multistate NLO switch for eventual exploitation in optical memory systems with multiple storage and nondestructive readout capacity.

Bondu|Flavie|F| Quertinmont|Jean|J| Rodriguez|Vincent|V| Pozzo|Jean-Luc|JL| Plaquet|Aurélie|A| Champagne|Benoît|B| Castet|Frédéric|F|

nonlinear optics
molecular switches
hyper-Rayleigh scattering
chromophores
quantum chemistry calculations


Effects of home visits for pregnant and postpartum women on premature birth, low birth weight and rapid repeat birth: a meta-analysis and systematic review of randomized controlled trials.

Abstract:
BACKGROUND
Home visits seem promising for improving the health of women and infants during pregnancy and postpartum. This review aimed to quantitatively analyse the effects of home visits delivered during pregnancy and postpartum on premature birth (PTB), low birth weight (LBW) and rapid repeat birth (RRB).

METHODS
Literature was retrieved from PubMed, EMBASE, Web of Science and the Cochrane Library from January 1960 to October 2018 and the references lists of related studies and reviews were also screened. Eligible papers were randomized controlled trials (RCTs) that focussed on home visits conducted with women during pregnancy or postpartum and reported at least one of the following results: PTB, LBW and RRB. Fixed- or random-effects models were used to analyse the pooled results.

RESULTS
Fourteen RCTs were included. Pooled estimates showed a beneficial effect on LBW (odds ratio (OR) = 0.83; P = 0.03; low-quality evidence) and RRB in the professional-visit subgroup (OR = 0.62; P = 0.003; moderate-quality evidence). However, there was insufficient evidence to support the favourable effects of home visits on PTB (OR = 0.96; P = 0.59, moderate-quality evidence) and RRB in the non-professional-visit subgroup (OR = 0.86; P = 0.53, moderate-quality evidence). The overall methodological quality was moderate. Egger's test suggested no publication bias for PTB and LBW.

CONCLUSION
This meta-analysis is the first to suggest that home visits can prevent and decrease LBW and RRB; however, it remains unclear whether home visits benefit PTB. Therefore, home visits can be an alternative and complementary part of primary health care for women, especially those with risk factors.

Liu|Na|N| Li|Ping|P| Wang|Jie|J| Chen|Dandan|D| Sun|Weijia|W| Zhang|Wei|W|

D016032:Randomized Controlled Trials as Topic

Home visits
premature birth
low birth weight
rapid repeat birth
meta-analysis
systematic review


First-in-human administration of a live-attenuated RSV vaccine lacking the G-protein assessing safety, tolerability, shedding and immunogenicity: a randomized controlled trial.

Abstract:
BACKGROUND
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in early infancy and in elderly. A pediatric vaccine against RSV would not only prevent morbidity and mortality amongst infants and young children but could also reduce transmission to elderly. The RSVΔG vaccine consists of a live-attenuated RSV that lacks the G attachment protein. RSVΔG is severely impaired in binding to host cells and exhibits reduced infectivity in preclinical studies. Intranasal immunization of cotton rats with RSVΔG vaccine protected against replication of wildtype RSV, without inducing enhanced disease.

METHODS
We performed a first-in-human trial with primary objective to evaluate safety and shedding of RSVΔG (6.5 log10 CCID50) after intranasal administration. Healthy adults aged between 18 and 50, with RSV neutralizing serum titers below 9.6 log2, received a single dose of either vaccine or placebo (n = 48, ratio 3:1). In addition to safety and tolerability, nasal viral load, and systemic and humoral immune responses were assessed at selected time points until 4 weeks after immunization.

RESULTS
Intranasal administration of RSVΔG was well tolerated with no findings of clinical concern. No infectious virus was detected in nasal wash samples. Similar to other live-attenuated RSV vaccines, neutralizing antibody response following inoculation was limited in seropositive adults.

CONCLUSIONS
A single dose of 6.5 log10 CCID50 of RSVΔG was safe and well-tolerated in seropositive healthy adults. RSVΔG was sufficiently attenuated but there were no signs of induction of antibodies. Safety and immunogenicity can now be explored in children and eventually in seronegative infants. Clinical trial register: NTR7173/EudraCT number 2016-002437-30.

Verdijk|Pauline|P|
van der Plas|Johan L|JL|
van Brummelen|Emilie M J|EMJ|
Jeeninga|Rienk E|RE|
de Haan|Cornelis A M|CAM|
Roestenberg|Meta|M|
Burggraaf|Jacobus|J|
Kamerling|Ingrid M C|IMC|

D018357:Respiratory Syncytial Virus Infections

D022261:Respiratory Syncytial Virus Vaccines

D018113:Respiratory Syncytial Virus, Human

Safety
Immunogenicity
Respiratory Syncytial Virus
Intranasal
Live-attenuated vaccine
phase I trial


Low-cost, flexible, and self-cleaning 3D nanocone anti-reflection films for high-efficiency photovoltaics.

Abstract: Low-cost engineered nanotemplates are used to mold flexible nanocone anti-reflection (AR) films. Both optical reflectance measurements and photovoltaics characterizations demonstrate that the flexible nanocone AR films can considerably suppress device front-side reflectance and thus improve the power conversion efficiency of high-efficiency thin-film CdTe solar cells. Additionally, these nanocone AR films are found to be superhydrophobic and thus possess self-cleaning capability.

Tsui|Kwong-Hoi|KH| Lin|Qingfeng|Q| Chou|Hungtao|H| Zhang|Qianpeng|Q| Fu|Huiying|H| Qi|Pengfei|P| Fan|Zhiyong|Z|

self-cleaning
nanocones
anti-reflection
CdTe solar cells
superhydrophobicity


Clostridium ventriculi bacteremia following acute colonic pseudo-obstruction: A case report.

Abstract: Clostridium ventriculi (formerly Sarcina ventriculi) is a Gram-positive, obligate anaerobic coccus. Human infections due to this bacterium have rarely been reported, its involvement in the development of gastric ulcers and perforation has been suggested. We present a case of bacteremia due to C. ventriculi following acute colonic pseudo-obstruction.

Bortolotti|Perrine|P|
Kipnis|Eric|E|
Faure|Emmanuel|E|
Faure|Karine|K|
Wacrenier|Agnès|A|
Fauquembergue|Maud|M|
Penven|Malo|M|
Messaadi|Sophian|S|
Marceau|Laure|L|
Dessein|Rodrigue|R|
Le Guern|Rémi|R|

Clostridium ventriculi
Bacteremia
Sarcina ventriculi
Ogilvie syndrome


Voluntary exercise reverses immune aging induced by oxidative stress in aging mice.

Abstract: Excessive oxidative stress leads to aging due to persistent damage to the cells, tissues, and the entire organism. Immunosenescence is also a devastating consequence of oxidative stress, but there is a lack of research on effective ways to overcome it. In this study, we used physiologic and immunological aging mouse models that had sustained oxidative stress to investigate whether voluntary exercise and/or antioxidant treatment could overcome oxidative damage as well as aging. We established an aging model induced by continuously administering d-galactose (d-gal) to 6-week-old female C57BL/6J mice. We also assessed reversal of immunosenescence by providing free-wheel running and vitamin E (vit E) supplementation to this aging model. As an aging index, the level of advanced glycation end products (AGEs) in the blood was measured. Phenotypes of T cells in the thymus and spleen were examined as an index of immunosenescence. Intracellular reactive oxygen species (ROS) levels in the mouse spleen and levels of AGEs in the blood were significantly higher after 6 weeks of d-gal administration. In addition, immunosenescence was observed, in which the naïve:effector cell ratio in the spleen decreased. After 4 weeks of free-wheel running and vit E administration, both intracellular ROS and serum AGE levels decreased. Above all, free-wheel running restored the naïve:effector ratio of cytotoxic T lymphocytes reduced by d-gal administration. Taken together, these results suggest that voluntary exercise may be effective in restoring immunosenescence induced by oxidative stress.

Lee|Ji-Young|JY|
Paik|Il-Young|IY|
Kim|Joo Young|JY|

D017127:Glycation End Products, Advanced

Voluntary exercise
Aging
Oxidative stress
Immunosenescence
Vitamin E


Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in patients with a previous myocardial infarction: a randomised controlled trial.

Abstract:
OBJECTIVE
The mechanisms through which ω-3 fatty acids reduce adverse cardiac events remain uncertain. We aimed to investigate the effect of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in patients with coronary heart disease.

DESIGN
Randomised, double-blind, placebo-controlled, cross-over trial.

SETTING
Academic cardiac centre.

PARTICIPANTS
20 male patients with a previous myocardial infarction.

INTERVENTION
ω-3 Fatty acid supplementation (2 g/day for 6 weeks) versus olive oil placebo.

OUTCOME MEASURES
Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 patients during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion.

RESULTS
All vasodilators caused dose-dependent increases in FBF (p<0.0001). ω-3 Fatty acid supplementation did not affect endothelium-dependent vasodilation with acetylcholine and substance P compared with placebo (p=0.5 and 0.9). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001), which was not affected by ω-3 fatty acid supplementation (p=0.9). ω-3 Fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40.

CONCLUSIONS
We have demonstrated that dietary supplementation with ω-3 fatty acids does not affect endothelial vasomotor function, endothelial t-PA release, or platelet and monocyte activation in patients with coronary heart disease. Cardiac benefits conferred by ω-3 fatty acids in coronary heart disease are unlikely to be mediated through effects on these systems.

Din|Jehangir N|JN|
Sarma|Jaydeep|J|
Harding|Scott A|SA|
Lyall|Karin|K|
Newby|David E|DE|
Flapan|Andrew D|AD|