Neural substrates involved in the cognitive information processing in teleost fish.

Abstract: Over the last few decades, it has been shown that fish, comprising the largest group of vertebrates and in many respects one of the least well studied, possess many cognitive abilities comparable to those of birds and mammals. Despite a plethora of behavioural studies assessing cognition abilities and an abundance of neuroanatomical studies, only few studies have aimed to or in fact identified the neural substrates involved in the processing of cognitive information. In this review, an overview of the currently available studies addressing the joint research topics of cognitive behaviour and neuroscience in teleosts (and elasmobranchs wherever possible) is provided, primarily focusing on two fundamentally different but complementary approaches, i.e. ablation studies and Immediate Early Gene (IEG) analyses. More recently, the latter technique has become one of the most promising methods to visualize neuronal populations activated in specific brain areas, both during a variety of cognitive as well as non-cognition-related tasks. While IEG studies may be more elegant and potentially easier to conduct, only lesion studies can help researchers find out what information animals can learn or recall prior to and following ablation of a particular brain area.

Cognition
Behaviour
IEG
Lesion studies
Learning
Neuroanatomy
Neuroethology


Verbal and spatial memory spans in mild cognitive impairment.

Abstract:
OBJECTIVES
Working memory (WM) for verbal and visual material may be affected early in individuals with mild cognitive impairment (MCI). Verbal and visuospatial span tasks, that is neuropsychological procedures commonly used for the clinical assessment of WM, have been scarcely investigated in these patients. Therefore, this study was aimed at evaluating whether performance on tests of verbal and visual-spatial span (which rely to different extents on distinct components of the WM system) is differently sensitive to the presence of MCI and, in particular, of a preclinical AD condition in patients with MCI.

MATERIALS & METHODS
99 patients with amnesic MCI were given the Digit Span Forward (DSF) and Digit Span Backward (DSB) tests and the Corsi span task (CS) at baseline and were followed up for two years. 32 MCI patients converted to Alzheimer's disease (MCIc), but 67 patients did not deteriorate to meet the criteria for AD (MCIs).

RESULTS
Results showed that although performance on DSF did not differ between groups, performance on DSB and CS and ratio indexes indicative of a performance decline passing from DSF to DSB and from DSF to CS significantly discriminated between a group of matched healthy controls and the overall group of MCI patients. Moreover, the ratio indexes significantly discriminated between MCIc and MCIs individuals.

CONCLUSIONS
These data are consistent with the hypothesis that individuals with MCI, particularly those destined to convert to AD, are affected by reduced central executive resources even though the phonological loop is still functioning normally.

D000544:Alzheimer Disease
D060825:Cognitive Dysfunction
D006801:Humans
D008570:Memory, Short-Term
D009483:Neuropsychological Tests
D065852:Spatial Memory

mild cognitive impairment
working memory
conversion
phonological loop and central executive


Multidrug-resistant Escherichia coli isolated from canine faeces in a public park in Quito, Ecuador.

Abstract:
OBJECTIVES
This study focused on estimating the prevalence of extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases, carbapenemases and MCR-1-producing Escherichia coli in canine faeces from a public park in Quito, Ecuador.

METHODS
Phenotypic and genotypic characterisation of E. coli isolated from 50 canine faecal samples recovered from a city park in Quito was performed. In addition, a multiple choice survey was conducted among 50 dog owners.

RESULTS
Of the 50 faecal samples, 20 (40.0%) presented E. coli resistant to ceftriaxone. Moreover, 23 E. coli isolates were recovered for further analysis. All of the isolates showed as multidrug-resistant (MDR) phenotype (resistant to three or more antibiotic families). Resistance to carbapenems, tigecycline and amikacin was not observed. No major clonal relatedness was observed among the resistant isolates. The ESBL genes blaCTX-M-15, blaCTX-M-55 and blaCTX-M-65 were the most common. Two isolates harboured the blaCMY-2 gene and one isolate harboured both mcr-1 and blaCTX-M-65. Statistical analysis showed that older people were more conscious of collecting and disposing of dog faeces than subjects aged <35 years (P < 0.05).

CONCLUSION
The finding of MDR E. coli in dog faeces in a city park in Ecuador illustrates the importance of analysing canine faeces in public settings (e.g. parks, playgrounds) as part of surveillance programmes for MDR E. coli. In addition, this research might be a sentinel sampling method to gain a better understanding of community sources of antibiotic-resistant Enterobacteriaceae at human-animal-environment interfaces.

Ortega-Paredes|David|D| Haro|Marco|M| Leoro-Garzón|Paula|P| Barba|Pedro|P| Loaiza|Karen|K| Mora|Francisco|F| Fors|Martha|M| Vinueza-Burgos|Christian|C| Fernández-Moreira|Esteban|E|

D024901:Drug Resistance, Multiple, Bacterial

Escherichia coli
Canine faeces
Public park
Ecuador
ESBL
mcr-1


Assessment of trace elements pollution in sea ports of New South Wales (NSW), Australia using macrophytobenthic plant Ecklonia radiata as a bio-indicator.

Abstract: In this study seaweeds (Ecklonia radiata) from six major sea ports of NSW, Australia were used as a bioindicator to assess the distribution and levels of trace elements accumulation in the ports compared to the background ecosystem. Bioconcentration ratio (BCR), biota sediment accumulation factor (BSAF), enrichment factor, multivariate statistical analysis and hierarchical cluster analysis were used to identify trace elements contamination. The results illustrate BCRs of Al, Fe, Mn, Zn, Pb, Cu, As and Ba in E. radiata whereas the BASFs portray boron enrichment in all sea ports along with bioaccumulation of As in Port Jackson and Pb in Port Botany. However, trace elements variations between studied and background locations was found to be significant for Port Kembla and Newcastle. The principal component analysis result explained four principal groups with 76.25% cumulative variance. Cluster analysis was further performed to detect major groups of elements and sites to portray interconnection between the contaminants and the locations.

D001315:Australia
D016000:Cluster Analysis
D017753:Ecosystem
D004784:Environmental Monitoring
D004787:Environmental Pollution
D019216:Metals, Heavy
D009517:New South Wales
D025341:Principal Component Analysis
D012624:Seaweed
D014131:Trace Elements
D014874:Water Pollutants, Chemical

Trace elements
Australia
Seaweed
Bioaccumulation
Seaports


Modelling energy and environmental impacts of traditional and improved shea butter production in West Africa for food security.

Abstract: This study improves the global application of methods and analyses, especially Life Cycle Assessment (LCA), that properly incorporates environmental impacts of firewood and a social sustainability indicator (human energy) as tools for sustainable human development. Specifically shea butter production processes, common throughout sub-Saharan Africa and crucial to food security, environmental sustainability, and women's empowerment, are analyzed. Many economic activities in the world rely on firewood for energy and labor that aren't included in traditional LCAs. Human energy (entirely from women) contributed 25-100% of shea butter production processes (2000-6100kJ/kg of shea butter) and mechanized production processes had reduced human energy without considerably greater total energy. Firewood accounted for 94-100% of total embodied energy (103 and 172MJ/kg of shea butter for improved and traditional shea butter production processes respectively) and global warming potential and 18-100% of human toxicity of the production processes. Implementation of improved cookstoves modeled in this study could reduce: (1) global warming potential by 78% (from 18 to 4.1kg CO2 eq/kg and 11 to 2.4kg CO2 eq/kg of shea butter for the traditional and improved processes respectively), (2) the embodied energy of using firewood by 52% (from 170 to 82MJ/kg and 103 to 49MJ/kg for the traditional and improved processes respectively), and (3) human toxicity by 83% for the non-mechanized traditional and improved processes (from 0.041 to 0.0071 1,4 DB eq/kg and 0.025 to 0.0042 1,4 DB eq/kg respectively). In addition, this is the first study to compare Economic Input-Output Life Cycle Assessment (EIO-LCA) and process-based LCA in a developing country and evaluate five traditional and improved shea butter production processes over different impact categories. Overall, this study developed a framework to evaluate and improve processes for achievement of the United Nation's Sustainable Development Goals for 2030 particularly to obtain food security.

Naughton|Colleen C|CC|
Zhang|Qiong|Q|
Mihelcic|James R|JR|

D003247:Conservation of Natural Resources

Food security
Life Cycle Assessment (LCA)
Human energy
Sub-Saharan Africa
Sustainable development
Gender
World oil crops


Incomplete atypical femoral fractures: assessing the diagnostic utility of DXA by extending femur length.

Abstract: Atypical femoral fractures (AFFs) are associated with prolonged bisphosphonate therapy. A feature of incomplete AFF is a localized periosteal reaction. It has been suggested that extending the length of the femur image at the time of dual-energy X-ray absorptiometry (DXA) may diagnose an incomplete AFF. In patients older than 50 yr on bisphosphonate therapy for more than 5 yr, we extended femur length at the time of routine DXA. Abnormal DXA images were suggested in 19 of 257 patients (7.4%). On X-ray, 7 patients (2.7%) showed no abnormality, 7 patients (2.7%) showed evidence of AFF, and 5 patients (2.0%) showed an unrelated radiographic abnormality. Of the 7 cases with X-ray evidence of AFF, 5 had a periosteal flare and 2 had a visible fracture line, both of whom needed insertion of an intramedullary nail. We demonstrated that it is feasible to detect incomplete AFF early using extended femur length imaging with a prevalence in our sample of 2.7% (95% confidence interval: 1.7%-3.7%).

McKenna|Malachi J|MJ|
van der Kamp|Susan|S|
Heffernan|Eric|E|
Hurson|Conor|C|

Atypical femoral fracture
DXA
bisphosphonate


Evolutionary adaptations in the flexor digitorum profundus muscle in Tamandua mexicana (Xenarthra, Myrmecophagidae).

Abstract: The northern tamandua (Tamandua mexicana) is a neotropical mammal of the order Pilosa, suborder Vermilingua, and family Myrmecophagidae. This species has anatomical and functional adaptations in its forelimb for semiarboreal quadrupedal locomotion. Several studies have reported that the medial head of the triceps brachii and flexor digitorum profundus muscles are fused in species belonging to the family Myrmecophagidae. However, there is no reference to the innervation in these. The triceps brachii muscle is commonly innervated by the radial nerve and the flexor digitorum profundus muscle by the ulnar and median nerves. This study aims to describe the gross anatomy of the flexor digitorum profundus muscle in Tamandua mexicana with respect to the shape, origin, insertion, innervation, and arterial supply. Both forelimbs of nine specimens were used, which were dissected from superficial to deep layers. The formalin-fixed caudomedial forearm muscles were weighed, and the weight percentages of individual forearm muscle specimens were calculated. The flexor digitorum profundus had the highest weight among the forearm muscles and consisted of five heads (three humerals, one radial, and one ulnar). These heads were innervated by median and ulnar nerves; therefore, based on the innervation pattern, we concluded that the medial head of the triceps brachii muscle is not fused with the flexor digitorum profundus. Therefore, the flexor digitorum profundus muscle is highly developed in Tamandua and occupies the caudal part of the arm and forearm, which is an evolutionary adaptation that could have occurred during evolution from the common ancestor of Tamandua and Myrmecophaga.

Vermilingua
anconeus epitrochlearis
myology
rete mirabile
thoracic limb


Ivabradine use in pregnant women-treatment indications and pregnancy outcome: an evaluation of the German Embryotox database.

Abstract:
PURPOSE
Ivabradine has been approved for the treatment of chronic heart failure and chronic stable angina pectoris in Europe. Based on adverse outcomes of reproductive animal studies and the lack of human data, ivabradine is considered contraindicated during pregnancy. The aim of this observational study is to analyse ivabradine use before and during pregnancy.

METHODS
We evaluated all ivabradine-related requests to the German Embryotox Institute from 2007 to 2019. Exposed pregnancies were analysed as to their outcome.

RESULTS
Off-label use for supraventricular tachycardia was frequent in women of childbearing age. Of 38 prospectively ascertained pregnancies with ivabradine exposure and completed follow-up, 32 resulted in live births, 3 in spontaneous abortions, and 3 were electively terminated. One neonate presented with major birth defects (atrial septal defect and cleft palate). In 33/38 patients, ivabradine was discontinued after confirmation of pregnancy without cardiac deterioration and 5/38 women continued ivabradine throughout pregnancy. In addition, there were 3 retrospectively reported pregnancies including one major birth defect (tracheal atresia).

CONCLUSION
This case series represents the largest cohort of ivabradine-exposed pregnancies, published so far. According to our findings, ivabradine appears not to be a major teratogen. However, established drugs of choice with strong evidence of low risk for the unborn should be preferred in women planning pregnancy. After inadvertent exposure during pregnancy or lack of treatment alternatives, fetal ultrasound for structural anomalies and growth restriction is recommended. In addition, close monitoring is necessary in pregnant women with supraventricular arrhythmias or cardiac disease.

Ivabradine
Pregnancy
Tachycardia
Drug safety
Reproductive age


Olfactory aversive conditioning during sleep reduces cigarette-smoking behavior.

Abstract: Recent findings suggest that novel associations can be learned during sleep. However, whether associative learning during sleep can alter later waking behavior and whether such behavioral changes last for minutes, hours, or days remain unknown. We tested the hypothesis that olfactory aversive conditioning during sleep will alter cigarette-smoking behavior during ensuing wakefulness. A total of 66 human subjects wishing to quit smoking participated in the study (23 females; mean age, 28.7 ± 5.2 years). Subjects completed a daily smoking diary detailing the number of cigarettes smoked during 7 d before and following a 1 d or night protocol of conditioning between cigarette odor and profoundly unpleasant odors. We observed significant reductions in the number of cigarettes smoked following olfactory aversive conditioning during stage 2 and rapid eye movement (REM) sleep but not following aversive conditioning during wakefulness (p < 0.05). Moreover, the reduction in smoking following aversive conditioning during stage 2 (34.4 ± 30.1%) was greater and longer lasting compared with the reduction following aversive conditioning during REM (11.9 ± 19.2%, p < 0.05). Finally, the reduction in smoking following aversive conditioning during sleep was significantly greater than in two separate control sleep experiments that tested aversive odors alone and the effects of cigarette odors and aversive odors without pairing. To conclude, a single night of olfactory aversive conditioning during sleep significantly reduced cigarette-smoking behavior in a sleep stage-dependent manner, and this effect persisted for several days.

Arzi|Anat|A| Holtzman|Yael|Y| Samnon|Perry|P| Eshel|Neetai|N| Harel|Edo|E| Sobel|Noam|N|


SARS-CoV-2 Infection and C-Section: A Prospective Observational Study.

Abstract: Pregnant women are particularly vulnerable to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In addition to unfavorable perinatal outcomes, there has been an increase in obstetric interventions. With this study, we aimed to clarify the reasons, using Robson's classification model, and risk factors for cesarean section (C-section) in SARS-CoV-2-infected mothers and their perinatal results. This was a prospective observational study that was carried out in 79 hospitals (Spanish Obstetric Emergency Group) with a cohort of 1704 SARS-CoV-2 PCR-positive pregnant women that were registered consecutively between 26 February and 5 November 2020. The data from 1248 pregnant women who delivered vaginally (vaginal + operative vaginal) was compared with those from 456 (26.8%) who underwent a C-section. C-section patients were older with higher rates of comorbidities, in vitro fertilization and multiple pregnancies (p < 0.05) compared with women who delivered vaginally. Moreover, C-section risk was associated with the presence of pneumonia (p < 0.001) and 41.1% of C-sections in patients with pneumonia were preterm (Robson's 10th category). However, delivery care was similar between asymptomatic and mild-moderate symptomatic patients (p = 0.228) and their predisposing factors to C-section were the presence of uterine scarring (due to a previous C-section) and the induction of labor or programmed C-section for unspecified obstetric reasons. On the other hand, higher rates of hemorrhagic events, hypertensive disorders and thrombotic events were observed in the C-section group (p < 0.001 for all three outcomes), as well as for ICU admission. These findings suggest that this type of delivery was associated with the mother's clinical conditions that required a rapid and early termination of pregnancy.

On Behalf Of The Spanish Obstetric Emergency Group|||

SARS-CoV-2
C-section
perinatal outcomes
pregnancy
pneumonia
delivery
COVID-19
Robson’s ten group


Women in India with Gestational Diabetes Mellitus Strategy (WINGS): Methodology and development of model of care for gestational diabetes mellitus (WINGS 4).

Abstract:
AIM
The Women In India with GDM Strategy (WINGS) project was conducted with the aim of developing a model of care (MOC) suitable for women with gestational diabetes mellitus (GDM) in low- and middle-income countries.

METHODOLOGY
The WINGS project was carried out in Chennai, Southern India, in two phases. In Phase I, a situational analysis was conducted to understand the practice patterns of health-care professionals and to determine the best screening criteria through a pilot screening study.

RESULTS
Phase II involved developing a MOC-based on findings from the situational analysis and evaluating its effectiveness. The model focused on diagnosis, management, and follow-up of women with GDM who were followed prospectively throughout their pregnancy. An educational booklet was provided to all women with GDM, offering guidance on self-management of GDM including sample meal plans and physical activity tips. A pedometer was provided to all women to monitor step count. Medical nutrition therapy (MNT) was the first line of treatment given to women with GDM. Women were advised to undergo fasting blood glucose and postprandial blood glucose testing every fortnight. Insulin was indicated when the target blood glucose levels were not achieved with MNT. Women were evaluated for pregnancy outcomes and postpartum glucose tolerance status.

CONCLUSIONS
The WINGS MOC offers a comprehensive package at every level of care for women with GDM. If successful, this MOC will be scaled up to other resource-constrained settings with the hope of improving lives of women with GDM.

Kayal|Arivudainambi|A|
Mohan|Viswanathan|V|
Malanda|Belma|B|
Anjana|Ranjit Mohan|RM|
Bhavadharini|Balaji|B|
Mahalakshmi|Manni Mohanraj|MM|
Maheswari|Kumar|K|
Uma|Ram|R|
Unnikrishnan|Ranjit|R|
Kalaiyarasi|Gunasekaran|G|
Ninov|Lyudmil|L|
Belton|Anne|A|

gestational diabetes mellitus
WINGS
model of care
management
pregnancy outcomes
Asian Indians
South Asians
screening and diagnosis


Measurement of cGMP-generating and -degrading activities and cGMP levels in cells and tissues: Focus on FRET-based cGMP indicators.

Abstract: The intracellular messenger molecule cGMP has an established function in the regulation of numerous physiological events. Yet for the identification of further biological cGMP-mediated functions, precise information whether a cGMP response exists in a certain cell type or tissue is mandatory. In this review, the techniques to measure cGMP i.e. cGMP-formation, -degradation or levels are outlined and discussed. As a superior method to measure cGMP, the article focusses on FRET-based cGMP indicators, describes the different cGMP indicators and discusses their advantages and drawbacks. Finally, the successful applications of these cGMP indicators to measure cGMP responses in cells and tissues are outlined and summarized. Hopefully, with the availability of the FRET-based cGMP indicators, the knowledge about the cGMP responses in special cells or tissues is going to increase thereby allowing to assess further cGMP-mediated functional responses and possibly to address their pathophysiology with the available guanylyl cyclase activators, stimulators and PDE inhibitors.

D031541:Fluorescence Resonance Energy Transfer

Guanylyl cyclase
Cyclic guanosine monophosphate
Fluorescence resonance energy transfer
Nitric oxide
Phosphodiesterase


IL-10 producing B cells regulated 1,3-β-glucan induced Th responses in coordinated with Treg.

Abstract: Repeated exposure to fungi-contaminated dust can lead to multiple adverse effects on the lung, such as hypersensitivity pneumonitis, granuloma even irreversible fibrosis. 1,3-β-glucan, a major cell wall component of fungi, is considered as its exposure biomarker. Existing studies showed that a series of Th responses were involved in 1,3-β-glucan induced hypersensitivity pneumonitis, in which macrophages, Treg, and IL-10 producing B cells were reported to participate. The reciprocal interaction among those critical immune cells in 1,3-β-glucan induced inflammation was not investigated yet. To clarify the regulatory mechanism of IL-10 producing B cells on Th and Treg, the current study set up a primary cell co-culture system. The anti-CD22 antibody was injected intraperitoneally to generate IL-10 producing B cells deficiency mouse model. Cells were isolated and purified from C57BL∖6 mice in different groups. Flow cytometry was used to check the phenotype of different cell subtypes. CBA assay and real-time PCR were used to examine the levels of multiple cytokines. Our results indicated that IL-10 producing B cells could modulate the 1,3-β-glucan induced inflammatory response. The modulation of IL-10 producing B cells on Th response after 1,3-β-glucan treatment was cell contact independent. What's more, the modulation pattern of IL-10 producing B cells might be impaired without Treg response. IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in co-ordination with Treg cells.

IL-10 producing B cells
1,3-β-glucan
Th responses
Treg
Inflammation


Patient and health professional satisfaction with an interdisciplinary patient safety program.

Abstract: Background Measuring humanistic outcomes is an important component of valuating healthcare services. There is a paucity of data on satisfaction with pharmacist implemented clinical services in long-term care settings. Objective To evaluate patient and health professional (HP) satisfaction with an interdisciplinary patient safety program performed in elderly patients with polypharmacy admitted to a long-term care hospital (LTCH). Method An interventional, longitudinal, prospective study was conducted in a Spanish LTCH. Pharmacist conducted the pharmacotherapy follow-up (reconciliation, pharmacotherapeutic optimization and educational interviews). Two satisfaction surveys were designed on a 10-point Likert-type scale. The patient survey was administered at discharge. The HP survey included the following dimensions: knowledge and program importance, pharmacist skills and pharmacist contributions to the interdisciplinary team. A reliability analysis was performed. Results 123 surveys were completed and returned; 74 patient surveys (response rate 97.4%) and 49 HP surveys (response rate 98.0%). The overall mean score of the patient survey was 9.46 ± 0.87, resulting in 82.4% very satisfied and 17.6% satisfied. The overall mean score of the HP survey was 8.85 ± 1.42, resulting in 65.3% very satisfied and 30.6% satisfied. Conclusion Elderly patients with polypharmacy and HPs reported high levels of satisfaction with the interdisciplinary patient safety program implemented in an LTCH. This positive response supports the value of pharmacists for managing older high-risk populations.

Health professional satisfaction
Patient safety
Long-term care
Elderly
Interdisciplinary care
Patient satisfaction
Pharmacotherapy quality improvement
Spain


Next generation sequencing in hematolymphoid neoplasia.

Abstract: Large scale sequencing projects over the past 2 decades have led to the identification of many common genomic alterations in hematolymphoid neoplasms, some of which with diagnostic, therapeutic, and prognostic implications [1-3]. Although these alterations can be tested individually with high sensitivity and specificity using dedicated single gene tests, it is increasingly impractical and costly to test them separately as the number of alterations grows. Instead, multiplex testing platforms that can test multiple targets in a specimen have been developed. Among these platforms, massively parallel sequencing technologies (so-called next-generation sequencing [NGS] [4]) prove to be most versatile and is increasingly being used to build tests to meet the clinical testing need. In hematolymphoid neoplasms, the early incorporation of molecular findings into the diagnostic criteria by WHO [5] has further accelerated the adoption of NGS-based tests in routine clinical practice. This article focuses on what is used in the clinical diagnostic laboratories today and is not intended to be a review of the NGS technology or its future direction. Following discussion of the 2 families of sequencing instruments from Illumina and Thermo Fisher and 3 target enrichment methods, aspects of the analysis and report of NGS results that is clinically relevant are discussed.

Next-generation sequencing
Leukemia
Molecular diagnostics


DMI-Fungicide Resistance in Venturia nashicola, the Causal Agent of Asian Pear Scab-How Reliable Are Mycelial Growth Tests in Culture?

Abstract: Scab, caused by Venturia nashicola, is among the most serious diseases of Asian pears and control of this disease largely relies on sterol demethylation inhibitor (DMI) fungicides. However, pear growers have complained about field performance of DMIs since the mid-2000s. In this study, to evaluate pathogen sensitivity, mycelial growth tests and inoculation tests were conducted using DMI-amended culture medium and fungicide-sprayed potted pear trees, respectively. Results confirmed distribution of isolates resistant to fenarimol, hexaconazole, and difenoconazole in the field populations. Importantly, results from tests in culture did not fully correlate with those from tests in planta. Due to phenotypic instability of resistance and poor sporulation of this pathogen in culture, resistance is generally assessed by laborious and time-consuming inoculation with conidia collected from a field. To improve the result interpretation from in vitro tests, the isolates were genotyped: the CYP51 gene which encodes the target sterol 14α-demethylase was sequenced and various mutations have been detected in the coding sequence of DMI-resistant isolates. In addition to the detected single nucleotide polymorphisms, alternative mechanisms, not based on changes in the structure of the target protein, may also increase DMI resistance. Development of molecular methods for the diagnosis of DMI resistance seems to be challenging in V. nashicola.

Ishii|Hideo|H|0000-0002-1827-8532
Cools|Hans Jorgen|HJ|
Nishimura|Kumiko|K|
Borghi|Lorenzo|L|0000-0002-9631-9694
Kikuhara|Kenji|K|
Yamaoka|Yuichi|Y|

Venturia nashicola
DMIs
CYP51
fungicide resistance
pear scab
sensitivity tests


Traumatic injuries associated with suicide attempts: A retrospective study from single national level 1 trauma center.

Abstract:
Background
Suicide is a complex phenomenon involving several risk factors. We aimed to describe the frequency, pattern, and outcomes of patients with traumatic injuries following suicide attempts admitted to a level 1 trauma center.

Methods
We conducted a retrospective analysis of data obtained from Qatar National Trauma Registry and mortuary database. The study included all patients with traumatic injuries following suicide attempts, admitted to the Hamad Trauma Center (HTC) from April 2008 to March 2018.

Results
During this 10-year period, 206 patients were admitted to the HTC for injuries associated with suicide attempts. The majority were males (76%), young age (mean age 31 years), and expatriates specifically from South Asia (55%). The most common injury was due to self-inflicted cutting and piercing (51%) followed by jumping from height (30%). Females chose jumping from high place more often as a method of suicide attempt (59% vs. 20%), while males chose self-stabbing or cutting their throat (59% vs. 25%) (P = 0.001). Most of the patients had head injuries (30%) that was severe in terms of abbreviated injury scale score (3.6 ± 0.9). More than half (54%) of the patients required psychiatric consultations. The in-hospital mortality was 8% which was comparable in both genders.

Conclusions
The present study revealed that 1.8% of trauma admissions at HTC were related to suicidal attempts. Better understanding of risk factors is important in devising preventive strategies.

Al-Thani|Hassan|H|
Mekkodathil|Ahammed|A|
Consunji|Rafael|R|
Mollazehi|Monira|M|
Ammar|Adham A|AA|
Parchani|Ashok|A|
Jogol|Hisham|H|
Hakim|Suhail Y|SY|
Kanbar|Ahad|A|
El-Menyar|Ayman|A|

traumatic injury
suicide
mortuary
Gender


Impact of intranasal application of nerve growth factor on the olfactory epithelium in rats with chemically induced diabetes.

Abstract: Recent studies suggest that nerve growth factor (NGF) protects olfactory cells and axons from injury in vitro. Eighteen Wistar-Albino rats randomly divided into three groups: control group, diabetic group without NGF, and diabetic with NGF. Intranasal NGF (6 µg/day) was administered over a 5-day period. At the end of 30 days, the olfactory epithelium (OE) of NGF-applied diabetic rats regenerated, the epithelium thickness was significantly higher, and caspase-3 expression was not significantly different from the control. The current results demonstrate that intranasally administered NGF significantly reversed OE morphological changes in diabetes by decreasing diabetes-related cell death and inflammation.

Yalim|Sidika|S| Dağlıoğlu|Kenan|K| Coskun|Gülfidan|G| Polat|Sait|S|

nerve growth factor
rat
Diabetes mellitus


Directed Differentiation of Human Embryonic Stem Cells Toward Placode-Derived Spiral Ganglion-Like Sensory Neurons.

Abstract: The ability to generate spiral ganglion neurons (SGNs) from stem cells is a necessary prerequisite for development of cell-replacement therapies for sensorineural hearing loss. We present a protocol that directs human embryonic stem cells (hESCs) toward a purified population of otic neuronal progenitors (ONPs) and SGN-like cells. Between 82% and 95% of these cells express SGN molecular markers, they preferentially extend neurites to the cochlear nucleus rather than nonauditory nuclei, and they generate action potentials. The protocol follows an in vitro stepwise recapitulation of developmental events inherent to normal differentiation of hESCs into SGNs, resulting in efficient sequential generation of nonneuronal ectoderm, preplacodal ectoderm, early prosensory ONPs, late ONPs, and cells with cellular and molecular characteristics of human SGNs. We thus describe the sequential signaling pathways that generate the early and later lineage species in the human SGN lineage, thereby better describing key developmental processes. The results indicate that our protocol generates cells that closely replicate the phenotypic characteristics of human SGNs, advancing the process of guiding hESCs to states serving inner-ear cell-replacement therapies and possible next-generation hybrid auditory prostheses. © Stem Cells Translational Medicine 2017;6:923-936.

Matsuoka|Akihiro J|AJ|
Morrissey|Zachery D|ZD|
Zhang|Chaoying|C|
Homma|Kazuaki|K|
Belmadani|Abdelhak|A|
Miller|Charles A|CA|
Chadly|Duncan M|DM|
Kobayashi|Shun|S|
Edelbrock|Alexandra N|AN|
Tanaka-Matakatsu|Miho|M|
Whitlon|Donna S|DS|
Lyass|Ljuba|L|
McGuire|Tammy L|TL|
Stupp|Samuel I|SI|
Kessler|John A|JA|

D000818:Animals
D001933:Brain Stem
D002454:Cell Differentiation
D002460:Cell Line
D019070:Cell Lineage
D002465:Cell Movement
D002470:Cell Survival
D018920:Coculture Techniques
D000066449:Human Embryonic Stem Cells
D006801:Humans
D051379:Mice
D058953:Neural Stem Cells
D051381:Rats
D011984:Sensory Receptor Cells
D013136:Spiral Ganglion

Embryonic stem cells
Stem cell
Cellular therapy
Neural differentiation
Neural induction
Progenitor cells
Transplantation


Microbial dynamics, metabolomic profiles, and the correlation between them during fermentation of serofluid dish.

Abstract:
BACKGROUND
Serofluid dish, a traditional Chinese fermented food, possesses unique flavors and health beneficial effects. These properties are likely due to the sophisticated metabolic networks during fermentation, which are mainly driven by microbiota. However, the exact roles of metabolic pathways and the microbial community during this process remain equivocal.

RESULTS
Here, we investigated the microbial dynamics by next-generation sequencing, and outlined a differential non-targeted metabolite profiling in the process of serofluid dish fermentation using the method of hydrophilic interaction liquid chromatography column with ultra-high-performance liquid chromatography-quadruple time-of-flight mass spectrometry. Lactobacillus was the leading genus of bacteria, while Pichia and Issatchenkia were the dominant fungi. They all accumulated during fermentation. In total, 218 differential metabolites were identified, of which organic acids, amino acids, sugar and sugar alcohols, fatty acids, and esters comprised the majority. The constructed metabolic network showed that tricarboxylic acid cycle, urea cycle, sugar metabolism, amino acids metabolism, choline metabolism, and flavonoid metabolism were regulated by the fermentation. Furthermore, correlation analysis revealed that the leading fungi, Pichia and Issatchenkia, were linked to organic acids, amino acid and sugar metabolism, flavonoids, and several other flavor and functional components. Antibacterial tests indicated the antibacterial effect of serofluid soup against Salmonella and Staphylococcus.

CONCLUSION
This work provides new insights into the complex microbial and metabolic networks during serofluid dish fermentation, and a theoretical basis for the optimization of its industrial production. © 2020 Society of Chemical Industry.

D002851:Chromatography, High Pressure Liquid

microbial dynamics
serofluid dish
correlation analysis
metabolite changes
metabolite network


The 60-kDa heat shock protein regulates energy rearrangement and protein synthesis to promote proliferation of multiple myeloma cells.

Abstract: To investigate the cellular mechanisms of multiple myeloma (MM), we used liquid chromatography-tandem mass spectrometry for proteomics analysis of CD138+ plasma cells from patients with MM and healthy controls. We found that the 60-kDa heat shock protein (HSP60, also known as HSPD1) was significantly upregulated in myeloma cells. HSP60 is an important chaperone protein that regulates the homeostasis of mitochondrial proteins and maintains mitochondrial function. Knockdown (KD) of HSP60 in myeloma cells resulted in inhibition of proliferation and reduced the quality of the mitochondria. Mitochondrial stress tests showed that HSP60 KD inhibited glycolysis and mitochondrial activity. Metabolomics showed a decrease in glycolysis and tricarboxylic acid cycle metabolites, and inhibited the formation of creatine and phosphocreatine by the reaction of S-adenosylmethionine (SAM) with amino acids mediated by demethyladenosine transferase 1, mitochondrial (TFB1M) and reduced energy storage substances. Moreover, HSP60 silencing influenced the synthesis of ribonucleotides and nicotinamide adenine dinucleotide phosphate (NADPH) by the pentose phosphate pathway to inhibit cell proliferation. HSP60 KD inhibited 5' adenosine monophosphate-activated protein kinase (AMPK), which inhibited the key enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), effecting the metabolism of fatty acids by inhibiting malonyl-coenzyme A. Our data suggest that reduced HSP60 expression alters metabolic reprogramming in MM, inhibits tumour progression and reduces mitochondrial-dependent biosynthesis, suggesting that HSP60 is a potential therapeutic target for MM treatment.

Wu|Xiaoxiao|X| Guo|Jianying|J| Chen|Yuling|Y| Liu|Xiaohui|X| Yang|Guangzhong|G| Wu|Yin|Y| Tian|Ying|Y| Liu|Nian|N| Yang|Lin|L| Wei|Songren|S| Deng|Haiteng|H| Chen|Wenming|W|0000-0001-6298-8489

D045744:Cell Line, Tumor
D049109:Cell Proliferation
D018834:Chaperonin 60
D004734:Energy Metabolism
D055785:Gene Knockdown Techniques
D006801:Humans
D024101:Mitochondrial Proteins
D009101:Multiple Myeloma
D009363:Neoplasm Proteins
D014176:Protein Biosynthesis


Using genetic variants to evaluate the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits: a Mendelian randomization study.

Abstract:
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has struck globally and is exerting a devastating toll on humans. The pandemic has led to calls for widespread vitamin D supplementation in public. However, evidence supporting the role of vitamin D in the COVID-19 pandemic remains controversial.

METHODS
We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effect of the 25-hydroxyvitamin D [25(OH)D] concentration on COVID-19 susceptibility, severity and hospitalization traits by using summary-level GWAS data. The causal associations were estimated with inverse variance weighted (IVW) with fixed effects (IVW-fixed) and random effects (IVW-random), MR-Egger, weighted edian and MR Robust Adjusted Profile Score (MR.RAPS) methods. We further applied the MR Steiger filtering method, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test and PhenoScanner tool to check and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic.

RESULTS
We found no evidence to support the causal associations between the serum 25(OH)D concentration and the risk of COVID-19 susceptibility [IVW-fixed: odds ratio (OR) = 0.9049, 95% confidence interval (CI) 0.8197-0.9988, p = 0.0473], severity (IVW-fixed: OR = 1.0298, 95% CI 0.7699-1.3775, p = 0.8432) and hospitalized traits (IVW-fixed: OR = 1.0713, 95% CI 0.8819-1.3013, p = 0.4878) using outlier removed sets at a Bonferroni-corrected p threshold of 0.0167. Sensitivity analyses did not reveal any sign of horizontal pleiotropy.

CONCLUSIONS
Our MR analysis provided precise evidence that genetically lowered serum 25(OH)D concentrations were not causally associated with COVID-19 susceptibility, severity or hospitalized traits. Our study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19.

Vitamin D
COVID-19
Susceptibility
Severity
Hospitalization
Mendelian randomization


Toward Wearable Energy Storage Devices: Paper-Based Biofuel Cells based on a Screen-Printing Array Structure.

Abstract: A novel paper-based biofuel cell with a series/parallel array structure has been fabricated, in which the cell voltage and output power can easily be adjusted as required by printing. The output of the fabricated 4-series/4-parallel biofuel cell reached 0.97±0.02 mW at 1.4 V, which is the highest output power reported to date for a paper-based biofuel cell. This work contributes to the development of flexible, wearable energy storage device.

Shitanda|Isao|I|0000-0001-9751-016X Momiyama|Misaki|M| Watanabe|Naoto|N| Tanaka|Tomohiro|T| Tsujimura|Seiya|S| Hoshi|Yoshinao|Y| Itagaki|Masayuki|M|

biofuel cells
biofuels
array structure
ink printing
paper-based device


TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) US clinical trial: Performance of a rapid deployment aortic valve.

Abstract:
BACKGROUND
The TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) trial (NCT01700439) evaluated the performance of the INTUITY rapid deployment aortic valve replacement (RDAVR) system in patients with severe aortic stenosis.

METHODS
TRANSFORM was a prospective, nonrandomized, multicenter (n = 29), single-arm trial. INTUITY is comprised of a cloth-covered balloon-expandable frame attached to a Carpentier-Edwards PERIMOUNT Magna Ease aortic valve. Primary and effectiveness endpoints were evaluated at 1 year.

RESULTS
Between 2012 and 2015, 839 patients underwent RDAVR. Mean age was 73.5 ± 8.3 years. Full sternotomy (FS) was used in 59% and minimally invasive surgical incisions in 41%. Technical success rate was 95%. For isolated RDAVR, mean crossclamp and cardiopulmonary bypass times for FS were 49.3 ± 26.9 minutes and 69.2 ± 34.7 minutes, respectively, and for minimally invasive surgical 63.1 ± 25.4 minutes and 84.6 ± 33.5 minutes, respectively. These times were favorable compared with Society of Thoracic Surgeons database comparators for FS: 76.3 minutes and 104.2 minutes, respectively, and for minimally invasive surgical, 82.9 minutes and 111.4 minutes, respectively (P < .001). At 30 days, all-cause mortality was 0.8%; valve explant, 0.1%; thromboembolism, 3.5%; and major bleeding, 1.3%. In patients with isolated aortic valve replacement, the rate of permanent pacemaker implantation was 11.9%. At 1 year, mean effective orifice area was 1.7 cm2; mean gradient, 10.3 mm Hg; and moderate and severe paravalvular leak, 1.2% and 0.4%, respectively.

CONCLUSIONS
INTUITY RDAVR performed effectively in this North American trial. It may lead to a relative reduction in aortic crossclamp time and cardiopulmonary bypass time and has excellent hemodynamic performance. Pacemaker implantation rate observed was somewhat greater than European trials and requires further investigation.

Barnhart|Glenn R|GR|
Accola|Kevin D|KD|
Grossi|Eugene A|EA|
Woo|Y Joseph|YJ|
Mumtaz|Mubashir A|MA|
Sabik|Joseph F|JF|
Slachman|Frank N|FN|
Patel|Himanshu J|HJ|
Borger|Michael A|MA|
Garrett|H Edward|HE|
Rodriguez|Evelio|E|
McCarthy|Patrick M|PM|
Ryan|William H|WH|
Duhay|Francis G|FG|
Mack|Michael J|MJ|
Chitwood|W Randolph|WR|
|||

D019918:Heart Valve Prosthesis Implantation

D019060:Minimally Invasive Surgical Procedures

aortic valve replacement
calcific aortic stenosis
minimally invasive surgery
rapid deployment valves
sutureless valves


In vitro evaluation of osteoblast adhesion, proliferation and differentiation on chitosan-TiO2 nanotubes scaffolds with Ca2+ ions.

Abstract: Hydrothermally synthesized TiO2 nanotubes (TNTs) were first used as a filler for chitosan scaffold for reinforcement purpose. Chitosan-TNTs (CTNTs) scaffolds prepared via direct blending and freeze drying retained cylindrical structure and showed enhanced compressive modulus and reduced degradation rate compared to chitosan membrane which experienced severe shrinkage after rehydration with ethanol. Macroporous interconnectivity with pore size of 70-230μm and porosity of 88% were found in CTNTs scaffolds. Subsequently, the functionalization of CTNTs scaffolds with CaCl2 solutions (0.5mM-40.5mM) was conducted at physiological pH. The adsorption isotherm of Ca2+ ions onto CTNTs scaffolds fitted well with Freundlich isotherm. CTNTs scaffolds with Ca2+ ions showed high biocompatibility by promoting adhesion, proliferation and early differentiation of MG63 in a non-dose dependent manner. CTNTs scaffolds with Ca2+ ions can be an alternative for bone regeneration.

Lim|Siew Shee|SS|
Chai|Chun Ye|CY|
Loh|Hwei-San|HS|

Chitosan-titanium dioxide nanotubes (CTNTs)


Hypergastrinemia Expands Gastric ECL Cells Through CCK2R+ Progenitor Cells via ERK Activation.

Abstract:
BACKGROUND & AIMS
Enterochromaffin-like (ECL) cells in the stomach express gastrin/cholecystokinin 2 receptor CCK2R and are known to expand under hypergastrinemia, but whether this results from expansion of existing ECL cells or increased production from progenitors has not been clarified.

METHODS
We used mice with green fluorescent protein fluorescent reporter expression in ECL cells (histidine decarboxylase [Hdc]-green fluorescent protein), as well as Cck2r- and Hdc-driven Tamoxifen inducible recombinase Cre (Cck2r-CreERT2, Hdc-CreERT2) mice combined with Rosa26Sor-tdTomato (R26-tdTomato) mice, and studied their expression and cell fate in the gastric corpus by using models of hypergastrinemia (gastrin infusion, omeprazole treatment).

RESULTS
Hdc-GFP marked the majority of ECL cells, located in the lower third of the gastric glands. Hypergastrinemia led to expansion of ECL cells that was not restricted to the gland base, and promoted cellular proliferation (Ki67) in the gastric isthmus but not in basal ECL cells. Cck2r-CreERT2 mice marked most ECL cells, as well as scattered cell types located higher up in the glands, whose number was increased during hypergastrinemia. Cck2r-CreERT2+ isthmus progenitors, but not Hdc+ mature ECL cells, were the source of ECL cell hyperplasia during hypergastrinemia and could grow as 3-dimensional spheroids in vitro. Moreover, gastrin treatment in vitro promoted sphere formation from sorted Cck2r+Hdc- cells, and increased chromogranin A and phosphorylated- extracellular signal-regulated kinase expression in CCK2R-derived organoids. Gastrin activates extracellular signal-regulated kinase pathways in vivo and in vitro, and treatment with the Mitogen-activated protein kinase kinase 1 inhibitor U0126 blocked hypergastrinemia-mediated changes, including CCK2R-derived ECL cell hyperplasia in vivo as well as sphere formation and chromogranin A expression in vitro.

CONCLUSIONS
We show here that hypergastrinemia induces ECL cell hyperplasia that is derived primarily from CCK2R+ progenitors in the corpus. Gastrin-dependent function of CCK2R+ progenitors is regulated by the extracellular signal-regulated kinase pathway.

Sheng|Weiwei|W|
Malagola|Ermanno|E|
Nienhüser|Henrik|H|
Zhang|Zhengyu|Z|
Kim|Woosook|W|
Zamechek|Leah|L|
Sepulveda|Antonia|A|
Hata|Masahiro|M|
Hayakawa|Yoku|Y|
Zhao|Chun-Mei|CM|
Chen|Duan|D|
Wang|Timothy C|TC|

Progenitor Cell
Enterochromaffin-Like (ECL) Cells
Gastrin
CCK2R or Gastrin Receptor
Cholecystokin-2 Receptor (CCK2R)
Chromogranin A (CgA)
Histidine Decarboxylase (Hdc)
Proton Pump Inhibitors (PPI)
Stem Cell Niche


Multilevel approaches to increase fruit and vegetable intake in low-income housing communities: final results of the 'Live Well, Viva Bien' cluster-randomized trial.

Abstract:
BACKGROUND
Fruit and vegetable (F&V) intake can reduce risks for chronic disease, but is much lower than recommended amounts in most Western populations, especially for those with low income levels. Rigorous research is needed on practical, cost-effective interventions that address environmental as well as personal determinants of F&V intake. This paper presents the results of a cluster randomized controlled trial evaluating the efficacy of 'Live Well, Viva Bien' (LWVB), a multicomponent intervention that included discount, mobile fresh F&V markets in conjunction with nutrition education.

METHODS
Fifteen subsidized housing sites in Providence County, Rhode Island (8 intervention and 7 control sites) were randomized using a random number generator. Of these, nine housed elderly and/or disabled residents and six housed families. A total of 1597 adult housing site residents (treatment n = 837; control n = 760) were enrolled (73% women, 54% Hispanic, 17% black, Mean age 54 years). A year-long multicomponent intervention including mobile F&V markets plus nutrition education (e.g. campaigns, DVDs, newsletters, recipes, and chef demonstrations) was implemented at intervention sites. Physical activity and stress interventions were implemented at control sites. Follow-up occurred at 6 and 12 months. The main outcome measure was F&V consumption measured by National Cancer Institute's 'Eating at America's Table All Day Screener'.

RESULTS
From baseline to 12 months, the intervention group increased total F&V intake by 0.44 cups with the control group decreasing intake by 0.08 cups (p < .02). Results also showed an increased frequency of F&V eating behaviors compared to the control group (p < .01). There was a clear dose response effect of the F&V markets with participants who reported attending all or most of the markets increasing F&V intake by 2.1 cups and 0.86 cups, respectively compared with less than half cup increases for lower levels of market attendance (p < .05). Use of the DVDs, recipes and taste-testings was also associated with greater increases in F&V intake; however, use of other educational components was not.

CONCLUSIONS
LWVB is the first cluster, randomized controlled trial to demonstrate the efficacy of year-round F&V markets on improving F&V intake for low-income adults, which provides an evidence-base to bolster the mission of mobile produce markets. Further, the results more broadly support investment in environmental changes to alleviate disparities in F&V consumption and diet-related health inequities.

TRIAL REGISTRATION NUMBER
Clinicatrials.gov registration number: NCT02669472.

Gans|Kim M|KM|0000-0003-3623-7790
Risica|Patricia Markham|PM|
Keita|Akilah Dulin|AD|
Dionne|Laura|L|
Mello|Jennifer|J|
Stowers|Kristen Cooksey|KC|
Papandonatos|George|G|
Whittaker|Shannon|S|
Gorham|Gemma|G|

Nutrition education, housing, community, food environment


Sensitivity of Claims-Based Algorithms to Ascertain Smoking Status More Than Doubled with Meaningful Use.

Abstract:
BACKGROUND
The "meaningful use of certified electronic health record" policy requires eligible professionals to record smoking status for more than 50% of all individuals aged 13 years or older in 2011 to 2012.

OBJECTIVES
To explore whether the coding to document smoking behavior has increased over time and to assess the accuracy of smoking-related diagnosis and procedure codes in identifying previous and current smokers.

METHODS
We conducted an observational study with 5,423,880 enrollees from the year 2009 to 2014 in the Truven Health Analytics database. Temporal trends of smoking coding, sensitivity, specificity, positive predictive value, and negative predictive value were measured.

RESULTS
The rate of coding of smoking behavior improved significantly by the end of the study period. The proportion of patients in the claims data recorded as current smokers increased 2.3-fold and the proportion of patients recorded as previous smokers increased 4-fold during the 6-year period. The sensitivity of each International Classification of Diseases, Ninth Revision, Clinical Modification code was generally less than 10%. The diagnosis code of tobacco use disorder (305.1X) was the most sensitive code (9.3%) for identifying smokers. The specificities of these codes and the Current Procedural Terminology codes were all more than 98%.

CONCLUSIONS
A large improvement in the coding of current and previous smoking behavior has occurred since the inception of the meaningful use policy. Nevertheless, the use of diagnosis and procedure codes to identify smoking behavior in administrative data is still unreliable. This suggests that quality improvements toward medical coding on smoking behavior are needed to enhance the capability of claims data for smoking-related outcomes research.

Huo|Jinhai|J|
Yang|Ming|M|
Tina Shih|Ya-Chen|YC|

D038801:International Classification of Diseases

sensitivity
smoking
administrative data
EHR


A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers.

Abstract: The main-protease (Mpro) catalyzes a crucial step for the SARS-CoV-2 life cycle. The recent SARS-CoV-2 presents the main protease (MCoV2pro) with 12 mutations compared to SARS-CoV (MCoV1pro). Recent studies point out that these subtle differences lead to mobility variances at the active site loops with functional implications. We use metadynamics simulations and a sort of computational analysis to probe the dynamic, pharmacophoric and catalytic environment differences between the monomers of both enzymes. So, we verify how much intrinsic distinctions are preserved in the functional dimer of MCoV2pro, as well as its implications for ligand accessibility and optimized drug screening. We find a significantly higher accessibility to open binding conformers in the MCoV2pro monomer compared to MCoV1pro. A higher hydration propensity for the MCoV2pro S2 loop with the A46S substitution seems to exercise a key role. Quantum calculations suggest that the wider conformations for MCoV2pro are less catalytically active in the monomer. However, the statistics for contacts involving the N-finger suggest higher maintenance of this activity at the dimer. Docking analyses suggest that the ability to vary the active site width can be important to improve the access of the ligand to the active site in different ways. So, we carry out a multiconformational virtual screening with different ligand bases. The results point to the importance of taking into account the protein conformational multiplicity for new promissors anti MCoV2pro ligands. We hope these results will be useful in prospecting, repurposing and/or designing new anti SARS-CoV-2 drugs.Communicated by Ramaswamy H. Sarma.

de Lima|Leonardo H F|LHF|https://orcid.org/0000-0003-4346-9880

SARS-CoV
metadynamics simulation
quantum calculations
COVID 19
multiconformational drug targeting


High-accuracy Detection of Preoperative Thyroid Nodules Using Combination of BRAFV600E Mutation and TMPRSS4 mRNA Level.

Abstract:
BACKGROUND
Papillary thyroid cancer (PTC) is the most common epithelial thyroid tumor, accounting for more than 80% of all thyroid cancers. Though the fine needle aspiration biopsy (FNAB) represents as the golden standard for the diagnostics of thyroid nodules, there is a ∼25% risk of indeterminate cytological features. TMPRSS4 is a newly found transmembrane serine protease which was overexpressed in papillary thyroid cancer (PTC).

AIMS
The aim of this study was to determine its potential as a diagnostic marker to improve the diagnostic accuracy of thyroid cancer.

METHODS
We used pyrosequencing and quantitative real-time PCR (qRT-PCT) approaches to examine BRAFV600E mutation and TMPRSS4 mRNA level in FNAB specimens of thyroid nodules. The detection and analysis were respectively applied to training group with 91, and test group with 88 samples.

RESULTS
We demonstrated that PTC patients had an increased TMPRSS4 mRNA level as compared with benign subjects. The diagnostic sensitivity, specificity, and accuracy of TMPRSS4 were 93.33, 100, and 96.70%, respectively. Notably, compared with BRAFV600E mutation testing alone, combining with TMPRSS4 mRNA level significantly increased the diagnostic sensitivity and accuracy.

CONCLUSIONS
Our findings indicated BRAFV600E mutation combination with TMPRSS4 mRNA analysis can dramatically improve the sensitivity and accuracy of preoperative diagnosis of thyroid nodules.

Zhang|Yanfang|Y| Zhang|Zhaoxia|Z| Ma|Jingjing|J| Pu|Jun|J| Hou|Peng|P| Yang|Qi|Q|

D000328:Adult
D044963:Biopsy, Fine-Needle
D004252:DNA Mutational Analysis
D005260:Female
D006801:Humans
D008297:Male
D008565:Membrane Proteins
D008875:Middle Aged
D009154:Mutation
D048493:Proto-Oncogene Proteins B-raf
D012333:RNA, Messenger
D012680:Sensitivity and Specificity
D012697:Serine Endopeptidases
D000077273:Thyroid Cancer, Papillary
D013964:Thyroid Neoplasms
D016606:Thyroid Nodule

Thyroid nodules
TMPRSS4
Papillary thyroid cancer (PTC)
Fine needle aspiration biopsy (FNAB)
BRAF(V600E) mutation


Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

Abstract:
BACKGROUND
Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis.

METHODS AND RESULTS
One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment (P<0.05). Compared with anti-TNF-α and cyclosporine, anti-IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (-25% versus -4% versus -2%), malondialdehyde (-27% versus +5% versus +26%), and NT-proBNP(-26% versus -13.6% versus 9.1%) and increase of fetuin-a (P<0.01). Pulse wave velocity and augmentation index were improved only after anti-IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting-untwisting (P<0.05).

CONCLUSIONS
In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment.

CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.

Ikonomidis|Ignatios|I| Papadavid|Evangelia|E| Makavos|George|G| Andreadou|Ioanna|I| Varoudi|Maria|M| Gravanis|Kostas|K| Theodoropoulos|Kostas|K| Pavlidis|George|G| Triantafyllidi|Helen|H| Moutsatsou|Paraskevi|P| Panagiotou|Christina|C| Parissis|John|J| Iliodromitis|Efstathios|E| Lekakis|John|J| Rigopoulos|Dimitrios|D|

interleukin-12
psoriasis
ustekinumab
pulse wave analysis
skin disease


Effect of palliative care training on perceived self-efficacy of the nurses.

Abstract:
BACKGROUND
Nurses are involved in providing end-of-life care for end stage individuals and their self-efficacy is one of the key factors bearing on such care. The purpose of this study was to determine the effect of palliative care on perceived self-efficacy of the nurses.

METHODS
This is a quasi-experimental study with pretest-posttest design. Sampling was randomized and included 40 individuals. The intervention consisted of palliative care training for four sessions, each lasting 45 min. Data were collected using demographic and perceived self-efficacy questionnaires completed before and after the intervention. Data were then analyzed by SPSS 16 software using descriptive and inferential statistics.

RESULTS
The mean age of the participants was 38.6 and their work experience was 14.25 years. The majority of the participants were female (85%) and had a bachelor level of education (92.5%). The findings showed that "perceived self-efficacy", "psychosocial support" and "symptom management" improved significantly after intervention (p < 0.05).

CONCLUSION
Based on the results, palliative care education has the potential to increase nurses' perceived self-efficacy. Since all members of the health care team Including nurses play an important role in providing palliative care, nursing managers can take an effective step to maximize the capacity of nurses by planning and supporting training in this regard.

Palliative care
Self-efficacy
Nurses
Symptom management
Psychological support


Long-Term Therapy Outcomes When Treating Chronic Kidney Disease Patients with Paricalcitol in German and Austrian Clinical Practice (TOP Study).

Abstract: Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients) from 2008 to 2013. Laboratory values, demographical, and clinical data were documented in 629 dialysis patients and 119 predialysis patients. In predialysis patients, median intact parathormone (iPTH) was 180.0 pg/mL (n = 105) at the start of the study, 115.7 pg/mL (n = 105) at last documentation, and 151.8 pg/mL (n = 50) at month 12, with 32.4% of the last documented iPTH values in the KDOQI (Kidney Disease Outcomes Quality Initiative) target range. In dialysis patients, median iPTH was 425.5 pg/mL (n = 569) at study start, 262.3 pg/mL (n = 569) at last documentation, and 266.1 pg/mL (n = 318) at month 12, with 36.5% of dialysis patients in the KDOQI target range. Intravenous paricalcitol showed more homogenous iPTH control than oral treatment. Combined analysis of all dialysis patients indicated comparable and stable mean serum calcium and phosphate levels throughout the study. Clinical symptoms, such as itching, bone pain, and fatigue, were improved compared with study entry. The spectrum and frequency of adverse events mirrored the known pattern for patients on dialysis. Paricalcitol is efficacious and has a consistent safety profile in sHPT over 12 months.

Obermüller|Nicholas|N|
Rosenkranz|Alexander R|AR|
Müller|Hans-Walter|HW|
Hidde|Dennis|D|
Veres|András|A|
Decker-Burgard|Sabine|S|
Weisz|Isolde|I|
Geiger|Helmut|H|

D050071:Bone Density Conservation Agents

paricalcitol
secondary hyperparathyroidism (sHPT)
chronic kidney disease (CKD)
dialysis
predialysis
parathormone (PTH)


Correlating 3D morphology with molecular pathology: fibrotic remodelling in human lung biopsies.

Abstract: Assessing alterations of the parenchymal architecture is essential in understanding fibrosing interstitial lung diseases. Here, we present a novel method to visualise fibrotic remodelling in human lungs and correlate morphological three-dimensional (3D) data with gene and protein expression in the very same sample. The key to our approach is a novel embedding resin that clears samples to full optical transparency and simultaneously allows 3D laser tomography and preparation of sections for histology, immunohistochemistry and RNA isolation. Correlating 3D laser tomography with molecular diagnostic techniques enables new insights into lung diseases. This approach has great potential to become an essential tool in pulmonary research.

Kellner|Manuela|M|
Wehling|Judith|J|
Warnecke|Gregor|G|
Heidrich|Marko|M|
Izykowski|Nicole|N|
Vogel-Claussen|Jens|J|
Lorbeer|Raoul-Amadeus|RA|
Antonopoulos|Georgios|G|
Janciauskiene|Sabina|S|
Grothausmann|Roman|R|
Knudsen|Lars|L|
Ripken|Tammo|T|
Meyer|Heiko|H|
Kreipe|Hans|H|
Ochs|Matthias|M|
Jonigk|Danny|D|
Kühnel|Mark Philipp|MP|

Allergic Alveolitis
Imaging/CT MRI etc
Interstitial Fibrosis


Novel method for evaluation of eye movements in patients with narcolepsy.

Abstract:
BACKGROUND
Narcolepsy causes abnormalities in the control of wake-sleep, non-rapid-eye-movement (non-REM) sleep and REM sleep, which includes specific eye movements (EMs). In this study, we aim to evaluate EM characteristics in narcolepsy as compared to controls using an automated detector.

METHODS
We developed a data-driven method to detect EMs during sleep based on two EOG signals recorded as part of a polysomnography (PSG). The method was optimized using the manually scored hypnograms from 36 control subjects. The detector was applied on a clinical sample with subjects suspected for central hypersomnias. Based on PSG, multiple sleep latency test and cerebrospinal fluid hypocretin-1 measures, they were divided into clinical controls (N = 20), narcolepsy type 2 (NT2, N = 19), and narcolepsy type 1 (NT1, N = 28). We investigated the distribution of EMs across sleep stages and cycles.

RESULTS
NT1 patients had significantly less EMs during wake, N1, and N2 sleep and more EMs during REM sleep compared to clinical controls, and significantly less EMs during wake and N1 sleep compared to NT2 patients. Furthermore, NT1 patients showed less EMs during NREM sleep in the first sleep cycle and more EMs during NREM sleep in the second sleep cycle compared to clinical controls and NT2 patients.

CONCLUSIONS
NT1 patients show an altered distribution of EMs across sleep stages and cycles compared to NT2 patients and clinical controls, suggesting that EMs are directly or indirectly controlled by the hypocretinergic system. A data-driven EM detector may contribute to the evaluation of narcolepsy and other disorders involving the control of EMs.

Christensen|Julie A E|JAE|
Kempfner|Lykke|L|
Leonthin|Helle L|HL|
Hvidtfelt|Mathias|M|
Nikolic|Miki|M|
Kornum|Birgitte Rahbek|BR|
Jennum|Poul|P|

D006970:Disorders of Excessive Somnolence

D047908:Intracellular Signaling Peptides and Proteins

Hypocretin versus non-hypocretin deficiency


Uncovering a unique path: Antidromic AVRT utilizing a left anteroseptal Mahaim-like accessory pathway.

Abstract: A 40-year-old man presented to our emergency department 2 hours after onset of shortness of breath, palpitations, and presyncope secondary to an adenosine-responsive wide complex tachycardia. Electrophysiology study was diagnostic for antidromic atrioventricular (AV) reentrant tachycardia utilizing a muscular connection from the anterior interventricular vein to the left ventricle with Mahaim-like properties, successfully treated with ablation in the distal coronary sinus (CS) system. This case highlights accessory pathways (a) with unique features (i.e., Mahaim-like characteristics) and (b) involving musculature from the distal CS system, thereby limiting the value of endocardial ablation for durable treatment. Importantly, the coronary venous system is an accessible vascular network for evaluation and catheter ablation of such arrhythmias.

Sandhu|Amneet|A|0000-0002-6435-5746
Tzou|Wendy S|WS|
Borne|Ryan T|RT|
Zipse|Matthew M|MM|0000-0002-5662-8505
Nguyen|Duy T|DT|0000-0001-6570-6010
Sauer|William H|WH|

D013611:Tachycardia, Atrioventricular Nodal Reentry


Partial arthroscopic trapeziectomy with or without ligament reconstruction to treat primary thumb carpometacarpal joint osteoarthritis.

Abstract: Many surgical options have been proposed for the treatment of first carpometacarpal (CMC1) osteoarthritis. Conventional techniques are invasive, so we wanted to develop an arthroscopic technique. Partial trapeziectomy combined with various interpositions and ligament reconstruction is a long-standing intervention. As in total trapeziectomy, the combination with ligament reconstruction remains controversial. The aim of this study was to demonstrate the benefits of adding an abductor pollicis longus (APL) ligament reconstruction to partial trapeziectomy performed under arthroscopy. This study analyzes the results of two consecutive case series carried out by a single surgeon. Thirty-four patients underwent an isolated partial trapeziectomy and 49 patients underwent partial trapeziectomy with ligament reconstruction using the APL. The patients were reviewed with an average follow-up of 3.7 years (13 months to 8.6 years) by an independent observer. The assessment included the analysis of pain, thumb appearance, QuickDASH score, Nelson Hospital score, and measurements of mobility and strength. For all patients, there was a marked reduction in pain (7.13 preoperatively vs.1.37 postoperatively) with 71% of patients having a painless thumb, the Nelson (11.14) and QuickDASH (17.89) scores as well as a clinical improvement in mobility and grip strength (14.5 KgF preop vs. 19.6 KgF postop) and key pinch (4.4 KgF preop vs. 5.4 KgF postop). The mean recovery time was 18.8 weeks. Eighty-four percent of patients were satisfied with the procedure with 90% having a stable thumb. No CRPS was found. However, the results were better for patients who underwent ligament reconstruction. There was a significant gain in grip strength, better first web opening and a lower percentage of painful thumbs. The other items were also slightly improved, but not significantly (Nelson Hospital score, QuickDASH score, key grip strength, percentage of stable thumbs, subjective thumb value estimated by patients). This technique is a less aggressive treatment of CMC1 osteoarthritis, with simplified and rapid rehabilitation. The addition of ligament reconstruction using the APL appears useful. The advantages of arthroscopy are a less painful postoperative course, low morbidity, ligament conservation, along with better access to remove loose bodies, osteophytes and to perform synovectomy. Partial trapeziectomy, which is especially indicated when the scaphotrapeziotrapezoid joint is not symptomatic, is much less used than total trapeziectomy; however, it is an attractive surgical option for young patients with significant functional demands. Arthroscopic partial trapeziectomy is a safe and reliable procedure.

Desmoineaux|P|P| Delaroche|C|C| Moslemi|A|A| Delcourt|T|T|

Thumb
Partial trapeziectomy
Arthroscopie
Arthroscopie
Arthroscopy
First carpometacarpal osteoarthritis
Ligamentoplastie
Ligamentoplasty
Pouce
Rhizarthrose
Trapézectomie partielle


Objective biomarkers for clinical relapse in multiple sclerosis: a metabolomics approach.

Abstract: Accurate determination of relapses in multiple sclerosis is important for diagnosis, classification of clinical course and therapeutic decision making. The identification of biofluid markers for multiple sclerosis relapses would add to our current diagnostic armamentarium and increase our understanding of the biology underlying the clinical expression of inflammation in multiple sclerosis. However, there is presently no biofluid marker capable of objectively determining multiple sclerosis relapses although some, in particular neurofilament-light chain, have shown promise. In this study, we sought to determine if metabolic perturbations are present during multiple sclerosis relapses, and, if so, identify candidate metabolite biomarkers and evaluate their discriminatory abilities at both group and individual levels, in comparison with neurofilament-light chain. High-resolution global and targeted 1H nuclear magnetic resonance metabolomics as well as neurofilament-light chain measurements were performed on the serum in four groups of relapsing-remitting multiple sclerosis patients, stratified by time since relapse onset: (i) in relapse (R); (ii) last relapse (LR) ≥ 1 month (M) to < 6 M ago; (iii) LR ≥ 6 M to < 24 M ago; and (iv) LR ≥ 24 M ago. Two hundred and one relapsing-remitting multiple sclerosis patients were recruited: R (n = 38), LR 1-6 M (n = 28), LR 6-24 M (n = 34), LR ≥ 24 M (n = 101). Using supervised multivariate analysis, we found that the global metabolomics profile of R patients was significantly perturbed compared to LR ≥ 24 M patients. Identified discriminatory metabolites were then quantified using targeted metabolomics. Lysine and asparagine (higher in R), as well as, isoleucine and leucine (lower in R), were shortlisted as potential metabolite biomarkers. ANOVA of these metabolites revealed significant differences across the four patient groups, with a clear trend with time since relapse onset. Multivariable receiver operating characteristics analysis of these four metabolites in discriminating R versus LR ≥ 24 M showed an area under the curve of 0.758, while the area under the curve for serum neurofilament-light chain was 0.575. Within individual patients with paired relapse-remission samples, all four metabolites were significantly different in relapse versus remission, with the direction of change consistent with that observed at group level, while neurofilament-light chain was not discriminatory. The perturbations in the identified metabolites point towards energy deficiency and immune activation in multiple sclerosis relapses, and the measurement of these metabolites, either singly or in combination, are useful as biomarkers to differentiate relapse from remission at both group and individual levels.

biomarker
relapse
multiple sclerosis
metabolomics
metabolites


Autoimmune arthritis in Ménière's disease: A systematic review of the literature.

Abstract:
INTRODUCTION
Successful management of patients with Ménière's disease (MD) involves understanding the pathophysiology of the disease and its comorbidities. The role of autoimmune diseases (AD) in MD remains unclear. The aim of this study was to further investigate the association between MD and AD. Specific goals were to characterize the prevalence, distribution, clinical and laboratory findings, and outcomes of autoimmune arthritis (AA) in MD.

EVIDENCE REVIEW
This systematic review was conducted according to PRISMA guidelines. Articles were identified through searches of MEDLINE, and EMBASE, as well as manual reviews of references, from 1947 to May 2017. We performed a systematic review of randomized-controlled trials (RCTs) and non-RCTs of cases of AA in MD. Due to the heterogeneity of the study methods and measures, a meta-analysis was not possible and a qualitative synthesis of the literature results was performed. The study protocol was registered with PROSPERO database (Trial Registration: CRD42017070516).

FINDINGS
A total of 237 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, nine studies were selected and subjected to a quality assessment. This quality control measure yielded eight studies for analysis in the systematic review. The prevalence of AA was higher in MD (1.0-10.0%) as compared to the general population (0-1.1%), and noted to be higher in patients with familial MD as compared to sporadic MD (16.9% vs 4.5%, p = 0.002). There was no evidence to suggest a difference in immunologic profiles or selected treatment regimens. The most commonly reported AA in patients with MD was rheumatoid arthritis with a mean point prevalence of 4.3%. Many studies did not standardize their diagnostic criteria and did not measure clinically meaningful outcomes.

CONCLUSIONS
There is a low level of evidence because of the lack of RCTs and original prospective studies. However, in this systematic review, we have identified the latest point prevalence data on AA in MD, indicating AA to be more prevalent within the MD population. RCTs treating MD as a local AD will enhance our understanding of the disease, and potentially change the way we manage MD.

Caulley|Lisa|L| Quimby|Alexandra|A| Karsh|Jacob|J| Ahrari|Azin|A| Tse|Darren|D| Kontorinis|Georgios|G|

Autoimmunity
Arthritis
Ménière’s disease
Vertigo


Whole and hemi-gland cryoablation for primary localized prostate cancer: Short and medium-term oncological and functional outcomes.

Abstract:
INTRODUCTION
To compare oncological, functional and post-operative outcomes of hemi (HC) vs. whole gland (WGC) cryoablation as first line treatment of localized prostate cancer.

MATERIAL AND METHOD
Sixty-six consecutive patients undertaking whole-gland cryoablation (WGC=40) or hemi-cryoablation (HC=26) in a tertiary referral centre between 2010 and 2018 were included. All patients had a low-intermediate risk prostate cancer according to D'Amico risk classification. Hemi-ablation was proposed in case of biopsy and prostate MRI proven unilateral prostate cancer. Primary endpoint was Cryotherapy Failure for which 3 definitions were considered and compared: 1) biochemical failure (> PSA nadir+≥ 2 ng/mL), 2) positive prostate re-biopsy with Gleason score ≥ 7, 3) initiation of further prostate cancer treatment.

RESULTS
Median patients age at treatment was 74 [42-81] vs. 76 [71-80] years in WGC vs. HC group, respectively (p=.08). Low and intermediate D'Amico risk group were 15% and 85% vs. 23% and 77% (p=.75), respectively. Median follow- up time was 41 [1.5-99.0] vs. 27 [0.9-93] months (p=.03). Four-years cryotherapy failure free survival in WGC vs. HC were 69% vs. 53% with definition 1 (p=.24), 82% vs. 80% with definition 2 (p=.95), 83% vs. 77% with definition 3 (p=.73). Early and 1-year urinary continence were 60% and 83% in WGC vs. 72% and 83% in HC (p=.26). De novo impotency after cryotherapy was 75% vs. 46% (p=.33) in WGC vs. HC.

CONCLUSIONS
In our cohort of highly selected patients with unilateral low/intermediate risk PCa, hemi-cryoablation may provide similar oncological outcomes and less early complications compared to whole-gland cryoablation.

Bossier|R|R|
Sanguedolce|F|F|
Territo|A|A|
Vanacore|D|D|
Martínez|C|C|
Regis|F|F|
Gallioli|A|A|
Mercade|A|A|
Mosquera|L|L|
Aumatell|J|J|
Balana|J|J|
Carlderon|J|J|
Huguet|J|J|
Gaya|J M|JM|
Palou|J|J|
Breda|A|A|

Prostate cancer
Cryotherapy
Crioterapia
Cáncer de próstata
Focal treatment
Tratamiento focal


Methods for Assessing the Role of Phloem Transport in Plant Stress Responses.

Abstract: Delivery of carbohydrates to tissues that need them under stress is important for plant defenses and survival. Yet, little is known on how phloem function is altered under stress, and how that influences plant responses to stress. This is because phloem is a challenging tissue to study. It consists of cells of various types with soft cell walls, and the cells show strong wounding reactions to protect their integrity, making both imaging and functional studies challenging. This chapter summarizes theories on how phloem transport is affected by stress and presents methods that have been used to gain the current knowledge. These techniques range from tracer studies and imaging to carbon balance and anatomical analyses. Advances in these techniques in the recent years have considerably increased our ability to investigate phloem function, and application of the new methods on plant stress studies will help provide a more comprehensive picture of phloem function and its limitations under stress.

Phloem
Stress
Tracer
Carbon balance
Drought
Hydraulic conductivity
Isotope
NMR
PET
Pathogen
Stem diameter variation


Fluctuations in eGFR in relation to unenhanced and enhanced MRI and CT outpatients.

Abstract:
OBJECTIVE
To study fluctuations in estimated glomerular filtration rate (eGFR) in relation to contrast medium (CM) enhanced magnetic resonance imaging (MRI) and computed tomography (CT) compared to control groups in outpatients.

MATERIALS AND METHODS
eGFR was determined right before the imaging procedure and three days later at the department or at the patient's home. The iodine-based and gadolinium-based contrast media were the same as used for all other examinations at the department.

RESULTS
A total of 716 patients completed the study. There was a statistically significant, but not clinically relevant rise in eGFR after three days in all four groups. The average eGFR variation was 4.8 ml/min/1.73 m(2). There were large variations in eGFR between the two measurements in 45.8% of the patients as they had a change greater than ± 10 ml/min/1.73 m(2). Only three patients fulfilled the contrast-induced nephropathy (CIN) requirement when the definition s-creatinine ≥ 44 μmol/l (0.5mg/dl) was used.

CONCLUSIONS
eGFR in outpatients undergoing MRI or CT did vary independently of whether the patient received contrast or not. The findings probably reflect the natural variations in s-creatinine levels. This should be taken into consideration when CIN is studied.

Azzouz|Manal|M|
Rømsing|Janne|J|
Thomsen|Henrik S|HS|

Fluctuations
eGFR
Outpatients
Gadolinium-based contrast media
CIN
Iodine-based contrast media


The Cardiac Pacemaker Clinic: Memories From a Bygone Era.

Abstract: In 1963, soon after the first ventricular pacemakers were implanted at the Royal Melbourne Hospital, attempts were made to identify impending pacing failure, thus preventing sudden death in these very vulnerable patients. By 1970, patient numbers had increased, a formal regular pacemaker clinic was established, and guidelines and protocols developed. The clinic was staffed by a physician, a biomedical engineer and cardiac technicians. The unipolar, asynchronous, non-programmable pulse generators were powered by mercuric oxide/zinc batteries and implanted in the abdomen, using either transvenous or epimyocardial leads. Although, pulse generators were electively replaced at 3 years, most had already been replaced because of power source depletion, electronic failure or lead issues. Testing in all patients involved an electrocardiographic rhythm strip and electronic analysis of the stimulus artefact using a calibrated high-speed storage oscilloscope. Results were compared to previous studies and significant changes were interpreted as impending power source depletion. As a result of this testing, 97% of cases of impending power source depletion were detected prior to failure. These findings allowed testing each 4 months and for pulse generator life to be extended beyond three years. With ventricular triggered pulse generators, new testing procedures were designed. With time, visiting regional centres and clinical evaluation of new products became important functions of the clinic.

D001145:Arrhythmias, Cardiac
D001315:Australia
D002304:Cardiac Pacing, Artificial
D004867:Equipment Design
D049673:History, 20th Century
D006801:Humans
D010138:Pacemaker, Artificial

Pacemaker
Pacemaker history
Pacemaker stimulus artefact
Pacemaker testing


A Novel Model for Nephrotic Syndrome Reveals Associated Dysbiosis of the Gut Microbiome and Extramedullary Hematopoiesis.

Abstract: Glomerular kidney disease causing nephrotic syndrome is a complex systemic disorder and is associated with significant morbidity in affected patient populations. Despite its clinical relevance, well-established models are largely missing to further elucidate the implications of uncontrolled urinary protein loss. To overcome this limitation, we generated a novel, inducible, podocyte-specific transgenic mouse model (Epb41l5), developing nephrotic syndrome in adult mice. Animals were comprehensively characterized, including microbiome analysis and multiplexed immunofluorescence imaging. Induced knockout mice developed a phenotype consistent with focal segmental glomerular sclerosis (FSGS). Although these mice showed hallmark features of severe nephrotic syndrome (including proteinuria, hypoalbuminemia and dyslipidemia), they did not exhibit overt chronic kidney disease (CKD) phenotypes. Analysis of the gut microbiome demonstrated distinct dysbiosis and highly significant enrichment of the Alistipes genus. Moreover, Epb41l5-deficient mice developed marked organ pathologies, including extramedullary hematopoiesis of the spleen. Multiplex immunofluorescence imaging demonstrated red pulp macrophage proliferation and mTOR activation as driving factors of hematopoietic niche expansion. Thus, this novel mouse model for adult-onset nephrotic syndrome reveals the significant impact of proteinuria on extra-renal manifestations, demonstrating the versatility of this model for nephrotic syndrome-related research.

Maier|Jasmin I|JI|0000-0003-4158-2935
Rogg|Manuel|M|0000-0002-6658-9159
Helmstädter|Martin|M|
Sammarco|Alena|A|
Walz|Gerd|G|
Werner|Martin|M|
Schell|Christoph|C|

nephrotic syndrome
gut microbiome
extramedullary hematopoiesis
EPB41L5
focal segmental glomerulosclerosis


The Efficacy of COGnitive tRaining in patiEnts with Amnestic mild coGnitive impairmENT (COG-REAGENT): Protocol for a Multi-Center Randomized Controlled Trial.

Abstract:
BACKGROUND
Amnestic mild cognitive impairment (aMCI) is often the prodromal stage of Alzheimer's disease (AD). Although previous studies have suggested that computerized cognitive training is an effective non-pharmacological intervention for aMCI, large-sample, randomized controlled studies are warranted to provide a high level of evidence.

OBJECTIVE
To identify the efficacy of computerized cognitive training for aMCI.

METHODS
This study will include 260 patients diagnosed with aMCI from 8 centers in China. A computerized multi-domain adaptive training program will be used in this study, and the targeted cognitive domains include memory, attention, language, and executive function. The patients will be randomized into either a cognitive-training group or an active-control group. The intervention is a 12-week internet-based cognitive training performed for 40 minutes per day, 4 days a week. Neuropsychological assessments and structural and functional MRI will be obtained at baseline, at the end of the intervention, and 6 months after randomization. The primary outcome will be the global cognitive function score assessed by Montreal Cognitive Assessment. The secondary outcomes include changes in other neuropsychological assessments and neuroplasticity changes measured by structural and functional MRI.

RESULTS
The trial is currently ongoing, and it is anticipated that recruitment will be completed in December 2020.

CONCLUSION
This multi-center, large-sample, randomized controlled trial will investigate the short and long-term effects of computerized cognitive training in patients with aMCI. Furthermore, the combination of functional and structural MRI results will also reveal the underlying mechanisms of the effect of intervention.

Xing|Yi|Y| Zhu|Zude|Z| Du|Yifeng|Y| Zhang|Junjian|J| Qu|Qiumin|Q| Sun|Li|L| Li|Yang|Y| Guo|Yanjun|Y| Peng|Guoping|G| Liu|Yong|Y| Yu|Yueyi|Y| Qiao|Yuchen|Y| Xie|Beijia|B| Shi|Xinrui|X| Lu|Jie|J| Jia|Jianping|J| Tang|Yi|Y|

D000647:Amnesia
D015928:Cognitive Behavioral Therapy
D060825:Cognitive Dysfunction
D006801:Humans
D009483:Neuropsychological Tests
D012107:Research Design
D016896:Treatment Outcome


Surfactants - Compounds for inactivation of SARS-CoV-2 and other enveloped viruses.

Abstract: We provide here a general view on the interactions of surfactants with viruses, with a particular emphasis on how such interactions can be controlled and employed for inhibiting the infectivity of enveloped viruses, including coronaviruses. The aim is to provide to interested scientists from different fields, including chemistry, physics, biochemistry, and medicine, an overview of the basic properties of surfactants and (corona)viruses, which are relevant to understanding the interactions between the two. Various types of interactions between surfactant and virus are important, and they act on different components of a virus such as the lipid envelope, membrane (envelope) proteins and nucleocapsid proteins. Accordingly, this cannot be a detailed account of all relevant aspects but instead a summary that bridges between the different disciplines. We describe concepts and cover a selection of the relevant literature as an incentive for diving deeper into the relevant material. Our focus is on more recent developments around the COVID-19 pandemic caused by SARS-CoV-2, applications of surfactants against the virus, and on the potential future use of surfactants for pandemic relief. We also cover the most important aspects of the historical development of using surfactants in combatting virus infections. We conclude that surfactants are already playing very important roles in various directions of defence against viruses, either directly, as in disinfection, or as carrier components of drug delivery systems for prophylaxis or treatment. By designing tailor-made surfactants, and consequently, advanced formulations, one can expect more and more effective use of surfactants, either directly as antiviral compounds or as part of more complex formulations.

Simon|Miriam|M| Veit|Michael|M| Osterrieder|Klaus|K| Gradzielski|Michael|M|

P P P M M M M M M M M M M M M M M M M M M M M M M M M R M M M


Temporary Treatment of Complex Subglottic Stenosis by an On-Site Customized Stent.

Abstract: Subglottic stenosis may be complex in shape, making challenging its treatment with standard commercially available stents. Personalized stents can lead to successful treatment; however they are not readily available due to the customization waiting time. We report the use of on-site customized temporary silicone stents for difficult benign subglottic stenosis in five patients unfit for surgery.

Andreetti|Claudio|C|
Poggi|Camilla|C|
Rendina|Erino Angelo|EA|
Fiorelli|Alfonso|A|

Subglottic stenosis
On-site customized stent
Airway stent


SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability.

Abstract: Atorvastatin, prescribed for the treatment of hypercholesterolemia, demonstrated overwhelming benefits in reducing cardiovascular morbidity and mortality. However, many patients discontinue therapy due to adverse reactions, especially myopathy. The Dutch Pharmacogenetics Working Group (DPWG) recommends an alternative agent to atorvastatin and simvastatin or a dose adjustment depending on other risk factors for statin-induced myopathy in SLCO1B1 rs4149056 CC or TC carriers. In contrast, the Clinical Pharmacogenetics Implementation Consortium (CPIC) published their guideline on simvastatin, but not on atorvastatin. In this work, we aimed to demonstrate the effect of SLCO1B1 phenotype and other variants (e.g., in CYP3A4/5, UGT enzymes or SLC transporters) on atorvastatin pharmacokinetics. For this purpose, a candidate-gene pharmacogenetic study was proposed. The study population comprised 156 healthy volunteers enrolled in atorvastatin bioequivalence clinical trials. The genotyping strategy comprised a total of 60 variants in 15 genes. Women showed higher exposure to atorvastatin compared to men (p = 0.001), however this difference disappeared after dose/weight (DW) correction. The most relevant pharmacogenetic differences were the following: AUC/DW and Cmax /DW based on (a) SLCO1B1 phenotype (p < 0.001 for both) and (b) CYP3A5*3 (p = 0.004 and 0.018, respectively). As secondary findings: SLC22A1 *2/*2 genotype was related to higher Cmax/DW (ANOVA p = 0.030) and SLC22A1 *1/*5 genotype was associated with higher Vd/F (ANOVA p = 0.032) compared to SLC22A1 *1/*1, respectively. Finally, UGT2B7 rs7439366 *1/*1 genotype was associated with higher tmax as compared with the *1/*3 genotype (ANOVA p = 0.024). Based on our results, we suggest that SLCO1B1 is the best predictor for atorvastatin pharmacokinetic variability and that prescription should be adjusted based on it. We suggest that the CPIC should include atorvastatin in their statin-SLCO1B1 guidelines. Interesting and novel results were observed based on CYP3A5 genotype, which should be confirmed with further studies.

SLCO1B1
atorvastatin
pharmacogenetics
precision medicine


The Effects of Money on Fake Rating Behavior in E-Commerce: Electrophysiological Time Course Evidence From Consumers.

Abstract: Online ratings impose significant effects on the behaviors of potential customers. Thus, online merchants try to adopt strategies that affect this rating behavior, and most of these strategies are connected to money, such as the strategies of returning cash coupons if a consumer gives a five-star rating (RI strategy, an acronym for "returning" and "if") or returning cash coupons directly with no additional requirements (RN strategy, an acronym for "returning" and "no"). The current study explored whether a certain strategy (RN or RI) was more likely to give rise to false rating behaviors, as assessed by event-related potentials. A two-stimulus paradigm was used in this experiment. The first stimulus (S1) was the picture of a product with four Chinese characters that reflected the product quality (slightly defective vs. seriously defective vs. not defective), and the second stimulus (S2) displayed the coupon strategy (RN or RI). The participants were asked to decide whether or not to give a five-star rating. The behavioral results showed that the RI strategy led to a higher rate of five-star ratings than the RN strategy. For the electrophysiological time courses, the N1, N2, and LPP components were evaluated. The slightly defective products elicited a larger amplitude of the N1 component than the seriously defective and not-defective products, reflecting that perceptual difficulty was associated with the processing of the slightly defective products. The RI strategy evoked a less negative N2 and a more positive LPP than the RN strategy, indicating that the subjects perceived less conflict and experienced stronger incentives when processing the RI strategy. These findings will benefit future studies of fake online comments and provide evidence supporting the policy of forbidding the use of the RI strategy in e-commerce.

Wang|Cuicui|C| Li|Yun|Y| Luo|Xuan|X| Ma|Qingguo|Q| Fu|Weizhong|W| Fu|Huijian|H|

money
fake rating behavior
N2
LPP
neuromarketing


Functional status and mortality at month and year in nonagenarians hospitalized due to acute medical illness.

Abstract:
OBJECTIVES
To analyze risk factors associated with short and long-term mortality in nonagenarians hospitalized due to acute medical conditions.

DESIGN, SETTING, AND PARTICIPANTS
Prospective study of all patients aged 90 years or older admitted in a geriatric unit during 2009 due to medical acute illness. Baseline variables were collected at admission (sex, cause of admission, Charlson index, serum albumin, functional, and mental status), functional loss at admission (as the difference between Barthel index(BI) 2 weeks before admission and BI at admission), and functional loss at discharge(as the difference between BI 2 weeks before admission and BI at discharge). The association of these variables with mortality at 1 month and 1 year after admission was analyzed by multivariate Cox regression analysis.

RESULTS
Out of all patients admitted, 434 (33%) were 90 years old or older and 76.3% were female. Mortality at 1 month and 1 year after admission was 19% and 57%, respectively. In the month mortality multivariate analysis, being older (HR, 1.11; 95% CI=1.02 to 1.20), a previous Barthel index less than 40 points (HR, 5.87; 95% CI=1.16 to 29.67), and functional loss at admission (HR; 1.13; 95% CI=1.03 to 1.25) were independent risk factors. When patients that died 1 month after admission were excluded, the presence of hypoalbuminemia <3g/dl (HR, 2.70; 95% CI=1.69 to 4.32) and functional loss at discharge (HR-1.08, 95% CI=1.03 to 1.14) were the factors associated with 1 year mortality.

CONCLUSIONS
In nonagenarians, functional impairment is the most important risk factor associated with short and long-term mortality after hospitalization due to acute medical illness.

Socorro García|Alberto|A|
de la Puente|María|M|
Perdomo|Beatriz|B|
López Pardo|Patricia|P|
Baztán|Juan J|JJ|

D000203:Activities of Daily Living
D000208:Acute Disease
D000369:Aged, 80 and over
D005260:Female
D016330:Frail Elderly
D017052:Hospital Mortality
D006760:Hospitalization
D006801:Humans
D053208:Kaplan-Meier Estimate
D008297:Male
D015999:Multivariate Analysis
D010351:Patient Discharge
D011446:Prospective Studies
D012044:Regression Analysis
D012307:Risk Factors


The endocannabinoid system: 'NO' longer anonymous in the control of nitrergic signalling?

Abstract: The endocannabinoid system (ECS) is a key cellular signalling system that has been implicated in the regulation of diverse cellular functions. Importantly, growing evidence suggests that the biological actions of the ECS may, in part, be mediated through its ability to regulate the production and/or release of nitric oxide, a ubiquitous bioactive molecule, which functions as a versatile signalling intermediate. Herein, we review and discuss evidence pertaining to ECS-mediated regulation of nitric oxide production, as well as the involvement of reactive nitrogen species in regulating ECS-induced signal transduction by highlighting emerging work supporting nitrergic modulation of ECS function. Importantly, the studies outlined reveal that interactions between the ECS and nitrergic signalling systems can be both stimulatory and inhibitory in nature, depending on cellular context. Moreover, such crosstalk may act to maintain proper cell function, whereas abnormalities in either system can undermine cellular homoeostasis and contribute to various pathologies associated with their dysregulation. Consequently, future studies targeting these signalling systems may provide new insights into the potential role of the ECS nitric oxide signalling axis in disease development and/or lead to the identification of novel therapeutic targets for the treatment of nitrosative stress-related neurological, cardiovascular, and metabolic disorders.

endocannabinoid system
nitric oxide
reactive nitrogen species
cannabinoid receptor
nitrosative stress