Solid-state NMR and EPR Spectroscopy of Mn2+ -Substituted ATP-Fueled Protein Engines.

Abstract: Paramagnetic metal ions deliver structural information both in EPR and solid-state NMR experiments, offering a profitable synergetic approach to study bio-macromolecules. We demonstrate the spectral consequences of Mg2+ / Mn2+ substitution and the resulting information contents for two different ATP:Mg2+ -fueled protein engines, a DnaB helicase from Helicobacter pylori active in the bacterial replisome, and the ABC transporter BmrA, a bacterial efflux pump. We show that, while EPR spectra report on metal binding and provide information on the geometry of the metal centers in the proteins, paramagnetic relaxation enhancements identified in the NMR spectra can be used to localize residues at the binding site. Protein engines are ubiquitous and the methods described herein should be applicable in a broad context.

Wiegand|Thomas|T|
Lacabanne|Denis|D|
Keller|Katharina|K|
Cadalbert|Riccardo|R|
Lecoq|Lauriane|L|
Yulikov|Maxim|M|0000-0003-3275-0714
Terradot|Laurent|L|
Jeschke|Gunnar|G|0000-0001-6853-8585
Meier|Beat H|BH|0000-0002-9107-4464
Böckmann|Anja|A|0000-0001-8149-7941

D004578:Electron Spin Resonance Spectroscopy

D019906:Nuclear Magnetic Resonance, Biomolecular

EPR spectroscopy
DNA replication
NMR spectroscopy
manganese
membrane proteins


Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy.

Abstract: Endometriosis can recur after either surgical or medical therapy. Long-term medical therapy is implemented to treat symptoms or prevent recurrence. Dienogest and gonadotropin-releasing hormone (GnRH) analogues with hormone add-back therapy seem to be equally effective for long-term treatment of pain symptoms associated with endometriosis. There is insufficient evidence to support the superiority of one therapy over the other. However, add-back hormone therapy (HT) is recommended for patients using GnRH agonists. The treatment selection depends on therapeutic effectiveness, tolerability, drug cost, the physician's experience, and expected patient compliance.

Bedaiwy|Mohamed A|MA|
Allaire|Catherine|C|
Alfaraj|Sukinah|S|

endometriosis
Dienogest
hormone add-back
GnRH-a
long term


The AbgT family: A novel class of antimetabolite transporters.

Abstract: The AbgT family of transporters was thought to contribute to bacterial folate biosynthesis by importing the catabolite p-aminobenzoyl-glutamate for producing this essential vitamin. Approximately 13,000 putative transporters of the family have been identified. However, before our work, no structural information was available and even functional data were minimal for this family of membrane proteins. To elucidate the structure and function of the AbgT family of transporters, we recently determined the X-ray structures of the full-length Alcanivorax borkumensis YdaH and Neisseria gonorrhoeae MtrF membrane proteins. The structures reveal that these two transporters assemble as dimers with architectures distinct from all other families of transporters. Both YdaH and MtrF are bowl-shaped dimers with a solvent-filled basin extending from the cytoplasm halfway across the membrane bilayer. The protomers of YdaH and MtrF contain nine transmembrane helices and two hairpins. These structures directly suggest a plausible pathway for substrate transport. A combination of the crystal structure, genetic analysis and substrate accumulation assay indicates that both YdaH and MtrF behave as exporters, capable of removing the folate metabolite p-aminobenzoic acid from bacterial cells. Further experimental data based on drug susceptibility and radioactive transport assay suggest that both YdaH and MtrF participate as antibiotic efflux pumps, importantly mediating bacterial resistance to sulfonamide antimetabolite drugs. It is possible that many of these AbgT-family transporters act as exporters, thereby conferring bacterial resistance to sulfonamides. The AbgT-family transporters may be important targets for the rational design of novel antibiotics to combat bacterial infections.

D015964:Gene Expression Regulation, Bacterial

antimetabolite transporters
membrane proteins
Alcanivorax borkumensis YdaH
Neisseria gonorrhoeae MtrF
AbgT-family transporters
X-ray crystallography


Predictive Role of Attachment, Coping, and Emotion Regulation in Gambling Motives of Adolescents and Young People.

Abstract: Gambling disorder may be linked with different gambling motives such as enhancement, social, and coping motives, and vulnerability factors such as attachment, emotion regulation and coping. The aim of this study was to measure the link between gambling motives and vulnerability factors in adolescents. The sample comprised 472 students recruited from high schools and vocational education centers (mean age 15.6, SD = 1.33). Gambling motives, gambling severity, parent and peer attachment, coping strategies, and difficulties in emotion regulation were assessed. The results showed that parent and peer attachment correlated with gambling motives (enhancement, social, and coping), whereas parent attachment predicted gambling motives. Difficulties of emotion regulation correlated with gambling motives, with lack of control standing out as the most significant predictor. Coping strategies also correlated with gambling motives, and maladaptive strategies predicted gambling motives. Additionally, gambling motives correlated with gambling severity, with coping and enhancement motives as predictors of gambling severity. Moreover, boys reported more enhancement motives and gambling severity than girls. Finally, difficulties in emotion regulation mediated the relationship between gambling motives and gambling severity. These results may be useful for prevention and intervention in gambling disorder in adolescents and young people.

Attachment
Coping
Emotion regulation
Gambling
Adolescents


Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms.

Abstract:
AIM
To examine the association between white opaque substance (WOS) and histologically verified lipid droplets in colorectal epithelial neoplasms.

METHODS
We reviewed colonoscopy records at our institution from 2014 to 2016 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms observed by magnifying narrow-band imaging (M-NBI) colonoscopy. Immunohistochemistry was used to stain tumors with a monoclonal antibody specific to adipophilin as a marker of lipids. The expression and distribution of adipophilin were compared between WOS-positive and WOS-negative lesions and among tumors classified by histologic type and depth of invasion.

RESULTS
Under M-NBI colonoscopy, 81 lesions were positive for WOS and 48 lesions were negative for WOS. The rate of adipophilin expression was significantly higher in WOS-positive lesions (95.1%) than in WOS-negative lesions (68.7%) (P = 0.0001). The incidence of deep adipophilin expression was higher in WOS-positive lesions (24.7%) than in WOS-negative lesions (4.2%) (P = 0.001). The incidence of deep expression was predominant among cancers with massive submucosal invasion (62.5%) compared to adenoma (7.2%) and high-grade dysplasia or cancers with slight submucosal invasion (12.7%) (P = 0.0001).

CONCLUSION
The distribution of lipid droplets may be closely associated with the visibility of WOS under M-NBI colonoscopy, and with histologic grade and depth of tumor invasion.

Kawasaki|Keisuke|K| Eizuka|Makoto|M| Nakamura|Shotaro|S| Endo|Masaki|M| Yanai|Shunichi|S| Akasaka|Risaburo|R| Toya|Yosuke|Y| Fujita|Yasuko|Y| Uesugi|Noriyuki|N| Ishida|Kazuyuki|K| Sugai|Tamotsu|T| Matsumoto|Takayuki|T|

D009375:Neoplasms, Glandular and Epithelial

White opaque substance
Magnifying narrow-band imaging
Adipophilin
Colorectal neoplasm
Magnifying endoscopy


Exploitation of virgin olive oil by-products (Olea europaea L.): phenolic and volatile compounds transformations phenomena in fresh two-phase olive pomace ('alperujo') under different storage conditions.

Abstract:
BACKGROUND
Much effort has recently been spent for re-using virgin olive oil by-products as nutraceutical ingredients for human diet thanks to their richness in bioactive phenols, but their management is not easy for producers. We aimed to provide useful information for a better management of fresh olive pomace before drying, by studying the phenolic and volatile compounds transformations phenomena of fresh olive pomace stored under different conditions planned to simulate controlled and uncontrolled temperature conditions in olive oil mills.

RESULTS
The evolution of the phenolic and volatile compounds was studied by high-performance liquid chromatography-diode array detector mass spectrometry (HPLC-DAD-MS) and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS). The phenolic profile varied rapidly during storage: the verbascoside content decreased about 70% after 17 days even at 4 °C, while the content of simple phenols such as hydroxytyrosol and caffeic acid increased over time. The low temperature was able to slow down these phenomena. A total of 94 volatile organic compounds (VOCs) were detected in the fresh olive pomace, with a prevalence of lipoxygenase (LOX) VOCs (78%), mainly aldehydes (19 490.9 μg kg-1 ) despite the higher number of alcohols. A decrease in LOX volatiles and a quick development of the ones linked to off-flavors (carboxylic acids, alcohols, acetates) were observed, in particular after 4 days of storage at room temperature. Only storage at 4 °C allowed these phenomena to be slowed down.

CONCLUSION
To preserve the natural phenolic phytocomplex of fresh olive pomace before drying and to avoid off-flavors development, storage in open containers must be avoided and a short storage in cold rooms (7-10 days) is to be preferred. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

nutraceuticals
HS-SPME-GC-MS
olive mill by-products
olive pomace storage
polyphenols
secoiridoids


A critical ethnography of communication processes involving the management of oral chemotherapeutic agents by patients with a primary diagnosis of colorectal cancer: study protocol.

Abstract:
AIM
To describe the protocol used to examine the processes of communication between health professionals, patients and informal carers during the management of oral chemotherapeutic medicines to identify factors that promote or inhibit medicine concordance.

BACKGROUND
Ideally communication practices about oral medicines should incorporate shared decision-making, two-way dialogue and an equality of role between practitioner and patient. While there is evidence that healthcare professionals are adopting these concordant elements in general practice there are still some patients who have a passive role during consultations. Considering oral chemotherapeutic medications, there is a paucity of research about communication practices which is surprising given the high risk of toxicity associated with chemotherapy.

DESIGN
A critical ethnographic design will be used, incorporating non-participant observations, individual semi-structured and focus-group interviews as several collecting methods.

METHODS
Observations will be carried out on the interactions between healthcare professionals (physicians, nurses and pharmacists) and patients in the outpatient departments where prescriptions are explained and supplied and on follow-up consultations where treatment regimens are monitored. Interviews will be conducted with patients and their informal carers. Focus-groups will be carried out with healthcare professionals at the conclusion of the study. These several will be analysed using thematic analysis. This research is funded by the Department for Employment and Learning in Northern Ireland (Awarded February 2012).

DISCUSSION
Dissemination of these findings will contribute to the understanding of issues involved when communicating with people about oral chemotherapy. It is anticipated that findings will inform education, practice and policy.

D000284:Administration, Oral
D000328:Adult
D000884:Anthropology, Cultural
D000970:Antineoplastic Agents
D002985:Clinical Protocols
D015179:Colorectal Neoplasms
D003142:Communication
D003657:Decision Making
D005260:Female
D017144:Focus Groups
D006801:Humans
D008137:Longitudinal Studies
D008297:Male
D008875:Middle Aged
D009660:Northern Ireland
D011369:Professional-Patient Relations

ethnography
communication
decision-making
nurses
oral chemotherapy
doctors
information-giving
observational methods
oncology


Evaluation of an Analogue of the Marine ε-PLL Peptide as a Ligand of G-quadruplex DNA Structures.

Abstract: ε-poly-l-Lysine (ε-PLL) peptide is a product of the marine bacterium Bacillus subtilis with antibacterial and anticancer activity largely used worldwide as a food preservative. ε-PLL and its synthetic analogue α,ε-poly-l-lysine (α,ε-PLL) are also employed in the biomedical field as enhancers of anticancer drugs and for drug and gene delivery applications. Recently, several studies reported the interaction between these non-canonical peptides and DNA targets. Among the most important DNA targets are the DNA secondary structures known as G-quadruplexes (G4s) which play relevant roles in many biological processes and disease-related mechanisms. The search for novel ligands capable of interfering with G4-driven biological processes elicits growing attention in the screening of new classes of G4 binders. In this context, we have here investigated the potential of α,ε-PLL as a G4 ligand. In particular, the effects of the incubation of two different models of G4 DNA, i.e., the parallel G4 formed by the Pu22 (d[TGAGGGTGGGTAGGGTGGGTAA]) sequence, a mutated and shorter analogue of the G4-forming sequence known as Pu27 located in the promoter of the c-myc oncogene, and the hybrid parallel/antiparallel G4 formed by the human Tel22 (d[AGGGTTAGGGTTAGGGTTAGGG]) telomeric sequence, with α,ε-PLL are discussed in the light of circular dichroism (CD), UV, fluorescence, size exclusion chromatography (SEC), and surface plasmon resonance (SPR) evidence. Even though the SPR results indicated that α,ε-PLL is capable of binding with µM affinity to both the G4 models, spectroscopic and SEC investigations disclosed significant differences in the structural properties of the resulting α,ε-PLL/G4 complexes which support the use of α,ε-PLL as a G4 ligand capable of discriminating among different G4 topologies.

ε-PLL
G-quadruplex DNA
c-myc oncogene
epsilon-poly-l-lysine
human telomere
marine peptide


Sleep deprivation due to shift work.

Abstract: Sleep deprivation due to shift work is related to perturbation of the sleep/wake cycle, associated with the modified activity/rest pattern. This may cause a significant disruption of circadian rhythms of biologic functions, driven by the body clock located in the suprachiasmatic nuclei of the hypothalamus. Shift and night workers have to change sleep times and strategies according to their duty periods; consequently, both sleep length and quality can be considerably affected depending on the variable start and finish times on different shifts. About 10% of night and rotating shift workers, aged between 18 and 65 years, have been estimated to have a diagnosable "shift-work sleep disorder," according to the International Classification of Sleep Disorders, version 2 (ICSD-2). In the long run, this may lead to persistent and severe disturbances of sleep, chronic fatigue and psychoneurotic syndromes, besides being a risk or aggravating factor for accidents, gastrointestinal, cardiovascular, and reproductive disorders, as well as, probably, for cancer. Preventive and corrective actions deal with the organization of shift schedules according to ergonomic criteria, careful health surveillance, appropriate education and training on effective countermeasures, in particular, sleep hygiene and napping.

D010561:Personnel Staffing and Scheduling

shift work
sleep/wake cycle
circadian rhythms
cancer
organization of shift schedules
napping
interindividual differences
night work
tolerance to shift work


Environmental Triggers of lrgA Expression in Streptococcus mutans.

Abstract: The cidAB and lrgAB operons of Streptococcus mutans encode proteins that are structurally similar to the bacteriophage lambda family of holin-antiholin proteins, which are believed to facilitate cell death in other bacterial species. Although their precise function is not known, cidAB and lrgAB are linked to multiple virulence traits of S. mutans, including oxidative stress tolerance, biofilm formation, and autolysis. Here we investigate the regulation of lrgAB which in S. mutans shows a complex dependence on growth conditions that is not fully understood. By combining single-cell imaging of a fluorescent gene reporter with microfluidic control of the extracellular environment, we identify specific environmental cues that trigger lrgA expression and characterize cell-to-cell heterogeneity in lrgA activity. We find that the very abrupt activation of lrgA at stationary phase is tightly synchronized across the population. This activation is controlled by a small number of inputs that are sensitive to growth phase: extracellular pyruvate, glucose, and molecular oxygen. Activation of lrgA appears to be self-limiting, so that strong expression of lrgA is confined to a short interval of time. lrgA is programmed to switch on briefly at the end of exponential growth, as glucose and molecular oxygen are exhausted and extracellular pyruvate is available. Our findings are consistent with studies of other bacteria showing that homologs of lrgAB participate, with input from lytST, in the reimport of pyruvate for anaerobic fermentative growth.

Ishkov|Ivan P|IP|
Ahn|Sang-Joon|SJ|
Rice|Kelly C|KC|
Hagen|Stephen J|SJ|

Streptococcus mutans
fluorescence
pyruvate
bimodality
catabolite repression
ccpA
gamma distribution
two-component systems


Investigation of the effect of EEG-BCI on the simultaneous execution of flight simulation and attentional tasks.

Abstract: Brain-computer interfaces (BCIs) are widely used for clinical applications and exploited to design robotic and interactive systems for healthy people. We provide evidence to control a sensorimotor electroencephalographic (EEG) BCI system while piloting a flight simulator and attending a double attentional task simultaneously. Ten healthy subjects were trained to learn how to manage a flight simulator, use the BCI system, and answer to the attentional tasks independently. Afterward, the EEG activity was collected during a first flight where subjects were required to concurrently use the BCI, and a second flight where they were required to simultaneously use the BCI and answer to the attentional tasks. Results showed that the concurrent use of the BCI system during the flight simulation does not affect the flight performances. However, BCI performances decrease from the 83 to 63 % while attending additional alertness and vigilance tasks. This work shows that it is possible to successfully control a BCI system during the execution of multiple tasks such as piloting a flight simulator with an extra cognitive load induced by attentional tasks. Such framework aims to foster the knowledge on BCI systems embedded into vehicles and robotic devices to allow the simultaneous execution of secondary tasks.

Flight simulator
Alertness
Vigilance
Brain computer interface
Electroencephalography


A systematic review of tools used to screen and assess for externalising behaviour symptoms in low and middle income settings.

Abstract:
Background
Mental health issues, often manifested as behavioural difficulties, in children are estimated to be high in low and middle-income countries (LMIC) settings. There is a paucity of definitive data due to a lack of well-validated tools to use across settings. This review aims to provide evidence on what tools are used and which have been adapted and validated in LMIC settings.

Methods
We performed a systematic review to identify tools used to assess or screen externalising behaviour problems in children and adolescents in LMIC and assess their cultural adaptations. We searched for studies measuring externalising behaviour in children from 0 to 19 years published up to September 2018. Articles were assessed to identify tools used and analysed using the Ecological Validity Framework.

Results
We identified 82 articles from over 50 LMICs who had studied externalising behaviour in children. Twenty-seven tools were identified, with a predominance of studies using tools from the USA and Europe. Most studies did not describe an adaptation and evaluation process, with only one study following recommended criteria. New tools were identified which both screen and assess externalising behaviour which have not yet been utilised across settings.

Conclusions
Although tools from the USA and Europe are often utilised to screen and assess for externalising behaviour problems in children in LMICs, the conceptual frameworks behind the use of these tools in other cultural contexts are not always carefully examined. In order to have valid data across cultures, we should aim to adapt and validate tools before use. Provision of processes to validate tools across LMIC settings would be beneficial.

review
screening
Assessment
behaviour
low and middle income
measurement
child
cross-cultural


CD200 has an important role in the differential diagnosis of mature B-cell neoplasms by multiparameter flow cytometry.

Abstract:
BACKGROUND
Multiparameter flow cytometry is a useful tool for the diagnostic evaluation of mature B-cell neoplasms (MBN). Recently, it has been shown that CD200 may improve the distinction between chronic lymphocytic leukemia (CLL; CD200+) and mantle cell lymphoma (MCL; CD200-), but the role of CD200 expression in atypical CLL and other MBN remains to be established.

METHODS
To address this issue, we investigated the expression of CD200 in 159 consecutive cases of MBN.

RESULTS
CD200 was strongly expressed in CLL and was revealed to be an excellent marker to distinguish CLL from MCL, even in cases of atypical CLL. However, lack of CD200 was not an exclusive finding of MCL, being also observed in other MBNs. Furthermore, CD200 was highly expressed in hairy cell leukemia, being useful in the differential diagnosis of lymphomas with villous lymphocytes. Herein, we propose an algorithm to classify CD5+ MBNs based on the expression of CD200, CD11c, heavy chain immunoglobulins, and Matutes score.

CONCLUSIONS
These results expand the understanding of the CD200 expression in MBNs, giving further support for the inclusion of this marker in the routine investigation by flow cytometry.

Sandes|Alex F|AF|
de Lourdes Chauffaille|Maria|M|
Oliveira|Cláudia Regina M C|CR|
Maekawa|Yumi|Y|
Tamashiro|Nair|N|
Takao|Tânia T|TT|
Ritter|Estela C|EC|
Rizzatti|Edgar G|EG|

D015451:Leukemia, Lymphocytic, Chronic, B-Cell

CD200
flow cytometry
chronic lymphocytic leukemia
mantle cell lymphoma
lymphoma


Genomic characterization of SARS-CoV-2 in Egypt.

Abstract:
Introduction
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the globe, causing a pandemic. In Egypt over 115,000 individuals were infected so far.

Objective
In the present study, the objective is to perform a complete genome sequence of SAR-CoV2 isolated from Egyptian coronavirus disease (COVID-19) patients.

Methods
Nasopharyngeal swabs were collected from 61 COVID-19 patients who attended at National Cancer Institute, Kasr Al-Aini Hospital and the army hospital. Viral RNA was extracted and whole genomic sequencing was conducted using Next Generation Sequencing.

Results
In all cases, the sequenced virus has at least 99% identity to the reference Wuhan 1. The sequence analysis showed 204 distinct genome variations including 114 missense mutations, 72 synonymous mutations, 1 disruptive in-frame deletion, 7 downstream gene mutations, 6 upstream gene mutations, 3 frame-shift deletions, and 1 in-frame deletion. The most dominant clades were G/GH/GR/O and the dominant type is B.

Conclusion
The whole genomic sequence of SARS-CoV2 showed 204 variations in the genomes of the Egyptian isolates, where the Asp614Gly (D614G) substitution is the most common among the samples (60/61). So far, there were no strikingly variations specific to the Egyptian population, at least for this set of samples.

Zekri|Abdel-Rahman N|AN|
Easa Amer|Khaled|K|
Hafez|Mohammed M|MM|
Hassan|Zeinab K|ZK|
Ahmed|Ola S|OS|
Soliman|Hany K|HK|
Bahnasy|Abeer A|AA|
Abdel Hamid|Wael|W|
Gad|Ahmad|A|
Ali|Mahmoud|M|
Ali Hassan|Wael|W|
Samir Madboly|Mahmoud|M|
Abdel Raouf|Ahmad|A|
Khattab|Ayman A|AA|
Salah El Din Hamdy|Mona|M|
Sherif Soliman|May|M|
Hamdi El Sissy|Maha|M|
Mohamed El Khateeb|Sara|S|
Hosny Ezzelarab|Moushira|M|
Fathalla|Lamiaa A|LA|
Abouelhoda|Mohamed|M|

D000087123:COVID-19 Nucleic Acid Testing

Nasopharyngeal swab
Next generation sequencing
Sars-CoV2
Real time PCR


Error bounds in diffusion tensor estimation using multiple-coil acquisition systems.

Abstract: We extend the diffusion tensor (DT) signal model for multiple-coil acquisition systems. Considering the sum-of-squares reconstruction method, we compute the Cramér-Rao bound (CRB) assuming the widely accepted noncentral chi distribution. Within this framework, we assess the effect of noise in DT estimation and other measures derived from it, as a function of the number of acquisition coils, as well as other system parameters. We show the applications of CRB in many actual problems related to DT estimation: we compare different gradient field setup schemes proposed in the literature and show how the CRB can be used to choose a convenient one; we show that for fiber-type anisotropy tensors the ellipsoidal area ratio (EAR) can be estimated with less error than other scalar factors such as the fractional anisotropy (FA) or the relative anisotropy (RA), and that for this type of anisotropy tensors, increasing the number of coils is equivalent to increasing the signal-to-noise ratio, i.e., the information of the different coils can be regarded as independent. Also, we present results showing the CRB of several parameters for actual DT-MRI data. We conclude that the CRB is a valuable tool to optimal experiment design in DT-related studies.

Beltrachini|Leandro|L|
von Ellenrieder|Nicolás|N|
Muravchik|Carlos Horacio|CH|

Noncentral chi distribution
Cramér–Rao bound
Measurement noise


eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse.

Abstract:
KEY POINTS
In muscular cells, eukaryotic initiation factor subunit f (eIF3f) activates protein synthesis by allowing physical interaction between mechanistic target of rapamycin complex 1 (MTORC1) and ribosomal protein S6 kinase 1 (S6K1), although its physiological role in animals is unknown. A knockout approach suggests that homozygous mice carrying a null mutation of the eIF3f gene fail to develop and consequently die at early embryonic stage, whereas heterozygous mice associated with a partial depletion of eIF3f gene grow normally and are phenotypically indistinguishable from wild-type mice. Heterozygous mice express reduced eIF3f mRNA and protein levels in skeletal muscles and show diminished muscle mass associated with a decrease in the protein synthesis rate and an inhibition of the MTORC1 pathway. During hindlimb immobilization, heterozygous eIF3f mice display an exacerbated immobilization-induced muscle atrophy associated with reduced protein synthesis. These results highlight the essential role of eIF3f during embryonic development and its involvement in muscular homeostasis via protein synthesis regulation.

ABSTRACT
Eukaryotic translation initiation factor 3, subunit F (eIF3f), a component of eIF3 complex, plays an important role in protein synthesis regulation, although its physiological functions are unknown. We generated and analysed mice carrying a null mutation in the eIF3f gene. We showed that homozygous eIF3f knockout fail to develop and that eIF3f-/- embryos die at an early stage of development but after the pre-implantation stage. However, disrupting one eIF3f allele does not affect growth, viability and fertility of heterozygous mice but, instead, reduces eIF3f mRNA and protein levels in all tissues examined. Although heterozygous mice are phenotypically indistinguishable from wild-type mice, they present a diminished body weight and a lean mass reduction associated with normal body size. Interestingly, skeletal muscles are mainly affected and display an altered cell size without modification of fibre number. Skeletal muscles of heterozygous mice show a deficiency in polysome content, a decrease in protein synthesis rate and an inhibition of the mechanistic target of rapamycin (MTOR) pathway. We then studied the effects of hindlimb immobilization that mimic muscle disuse on heterozygous mice aiming to further explore the involvement of eIF3f in protein synthesis. We found that eIF3f partial depletion amplifies muscle atrophy compared to wild-type mice. Mass and cross-sectional area decreases were associated with reduced MTOR pathway activation and protein synthesis rate. Taken together, our data indicate that eIF3f is essential for mice embryonic development and controls adult skeletal muscle mass via protein synthesis regulation in a MTOR-dependent manner.

D000818:Animals
D047108:Embryonic Development
D039621:Eukaryotic Initiation Factor-3
D005260:Female
D008297:Male
D008807:Mice, Inbred BALB C
D008810:Mice, Inbred C57BL
D008822:Mice, Transgenic
D018482:Muscle, Skeletal
D009133:Muscular Atrophy

protein synthesis
eIF3f knockout
MTOR
skeletal muscle homeostasis


Lessons learned from conventional animals: Encouragement to use specific-pathogen-free animals.

Abstract: Experimental rabbits provide evidence for translational research regarding the pathogenies or treatment of human diseases. We developed a novel method for regenerating the middle ear mucosa using autologous cultured nasal mucosal epithelial cell sheets, and evaluated the wound healing process in the middle ear mucosa of experimental rabbits. Nonetheless, vigilant microbiological monitoring of experimental animals is essential to effectively prevent a decline in their health conditions, which may affect the research results. We experimented with contamination of Pasteurella multocida in non-specific-pathogen-free (SPF) rabbits (without microbiological monitoring). Most non-SPF rabbits had otitis media, whereas SPF rabbits did not, which affected their results during the mucosal regeneration study. The contamination was resolved by changing the experimental design from using non-SPF rabbits to that using SPF rabbits. It is crucial to use the SPF animals for any surgical intervention studies.

Morino|Tsunetaro|T| Kikuchi|Shun|S| Inagaki|Taro|T| Komori|Manabu|M| Yamamoto|Kazuhisa|K| Kojima|Hiromi|H| Yamato|Masayuki|M|

Vigilant microbiological monitoring
Otitis media
Mucosal regeneration study
Non-specific-pathogen-free rabbits
P. multocida, Pasteurella multocida
Pasteurella multocida contamination
SPF, specific-pathogen-free
Sinusitis


Deciphering functional biomolecule potential of marine diatoms through complex network approach.

Abstract: Marine diatoms are unique reservoirs of bioactive compounds having enormous applications in therapeutics. But high-throughput screening methods are needed to elucidate the interaction between numerous biomolecules and their targets, facilitating rapid screening for novel drug molecules. So, in the present study chemical constituents were extracted from five marine diatoms using un-targeted metabolite profiling and in-silico virtual screening bioinformatics was employed to predict their bioactivity and molecular targets. A total of 17 chemical constituents out of 51 showed interactions with 76 protein targets associated with 213 pathways. Ingredient-target-pathway network revealed oleic acid, linoleic acid and cholest-5-en-3-ol as major active constituents. Core subnetwork and protein association network showed involvement of these compounds in key metabolic pathways related to cell signaling, cell growth and metabolism of xenobiotics. Thus, the present study for the first time revealed the main active ingredients and their associated pathways from marine diatoms using complex network approach.

Marella|Thomas Kiran|TK|
Bansal|Hina|H|
Bhattacharjya|Raya|R|
Himanshu|||
Parmar|Nitesh|N|
Chaurasia|Ankur|A|
Watanabe|Makoto M|MM|
Bhatnagar|Amit|A|
Tiwari|Archana|A|

Diatoms
Complex network approach
Bioactive compounds
Pathway analysis


Cerebrospinal Fluid Biomarkers of Cognitive Decline in Parkinson's Disease.

Abstract: Among the nonmotor symptoms in Parkinson's disease (PD), cognitive impairment is one of the most common and devastating. Over recent years, mild cognitive impairment (MCI) has become a recognized feature of PD (PD-MCI). The underlying mechanisms which influence onset, rate of decline, and conversion to dementia (PDD) are largely unknown. Adding to this uncertainty is the heterogeneity of cognitive domains affected. Currently there are no disease-modifying treatments that can slow or reverse this process. Identification of biomarkers that can predict rate and risk of cognitive decline is therefore an unmet need. Cerebrospinal fluid (CSF) is an ideal biomarker candidate as its constituents reflect the metabolic processes underlying the functioning of brain parenchyma. The pathological hallmark of PD is the presence of aggregated α-synuclein (α-Syn) in intracellular Lewy inclusions. In addition, there is concomitant Alzheimer's disease (AD) pathology. In AD, decreased CSF β-amyloid 1-42 (Aβ42) and increased CSF tau levels are predictive of future cognitive decline, setting a precedent for such studies to be carried out in PD. CSF studies in PD have focused on the classical AD biomarkers and α-Syn. Longitudinal studies indicate that low levels of CSF Aβ42 are predictive of cognitive decline; however, results for tau and α-Syn were not consistent. This chapter summarizes recent findings of CSF biomarker studies and cognitive dysfunction in PD.

Cerebrospinal fluid
Biomarkers
Parkinson's disease
Cognitive impairment
Dementia


Short-term effects of particle gamma radiation activities on pulmonary function in COPD patients.

Abstract:
BACKGROUND
It is not known whether environmental gamma radiation measured in US cities has detectable adverse health effects. We assessed whether short-term exposure to gamma radiation emitted from ambient air particles [gamma particle activity (PRγ)] is associated with reduced pulmonary function in chronic obstructive pulmonary disease (COPD) patients.

OBJECTIVE
We hypothesize that the inhalation of gamma radiation emitted from ambient air particles may be associated with reduced pulmonary function in individuals with COPD.

METHODS
In 125 patients with COPD from Eastern Massachusetts who had up to 4 seasonal one-week assessments of particulate matter ≤2.5 μm (PM2.5), black carbon (BC), and sulfur followed by spirometry. The US EPA continuously monitors ambient gamma (γ) radiation including γ released from radionuclides attached to particulate matter that is recorded as 9 γ-energy spectra classes (i = 3-9) in counts per minute (CPMγ) in the Boston area (USA). We analyzed the associations between ambient and indoor PRγi (up to one week) and pre and post-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) and with forced vital capacity (FVC) using mixed-effects regression models. We estimated indoor PRγi using the ratio of the indoor-to-outdoor sulfur in PM2.5 as a proxy for infiltration of ambient radionuclide-associated particles.

RESULTS
Overall, exposures to ambient and indoor PRγi were associated with a similar decrease in pre- and post-BD FEV1 and FVC. For example, ambient PRγ3 exposure averaged from the day of pulmonary function testing through the previous 3 days [IQR of 55.1 counts per minute (CPMγ)] was associated with a decrease in pre-BD FEV1 of 21.0 ml (95%CI: -38.5 to -3.0 ml; p < 0.01) and pre-BD FVC of 27.5 ml [95% confidence interval (CI): -50.7 to -5.0 ml; p < 0.01] with similar effects adjusting for indoor and outdoor BC and PM2.5.

CONCLUSION
Our results show that short-term ambient and indoor exposures to environmental gamma radiation associated with particulate matter are associated with reduced pre- and post-BD pulmonary function in patients with COPD.

Vieira|Carolina L Z|CLZ|
Koutrakis|Petros|P|
Huang|Shaodan|S|
Grady|Stephanie|S|
Hart|Jaime E|JE|
Coull|Brent A|BA|
Laden|Francine|F|
Requia|Weeberb|W|
Schwartz|Joel|J|
Garshick|Eric|E|

D029424:Pulmonary Disease, Chronic Obstructive

Pulmonary function
Chronic obstructive pulmonary disease
Ambient and indoor air pollution
Background gamma radiation


Aqueous-phase oxidation of syringic acid emitted from biomass burning: Formation of light-absorbing compounds.

Abstract: Syringic acid is a methoxyphenol model compound derived from biomass burning, and its photooxidation processes have important effects on atmospheric chemistry. However, its aqueous-phase photochemistry remains unclear. In this study, we systematically report the photooxidation of syringic acid induced by OH radicals in the aqueous phase. Employing the relative rate technique, the bimolecular rate constant for syringic acid reaction with OH radicals was acquired to be (1.1 ± 0.3) × 1010 M-1 s-1. Notably, colored products were formed as the reaction progressed. Furthermore, the UV-vis and fluorescence spectra confirmed the formation of light-absorbing organic species, and the results agreed well with previous results on atmospheric and natural humic-like substances (HULIS). The photooxidation products were detected by high performance liquid chromatography mass spectrometry (HPLC/MS), and a possible reaction mechanism was proposed. The aqueous-phase reaction of syringic acid would undergo functionalization process forming a hydroxylation product that enhances the degree of oxidation of aqueous secondary organic aerosol (aqSOA), and goes through dimerization process by C-C or C-O coupling of phenoxy radicals which may conduce to the formation of HULIS. These findings suggest that the photooxidation of syringic acid is an important pathway for highly oxygenated phenolic aqSOA formation, providing a secondary source for HULIS in a liquid phase or in deliquescent particles surrounded by a layer of water.

Li|Fenghua|F|
Tsona|Narcisse T|NT|
Li|Jianlong|J|
Du|Lin|L|

Syringic acid
Biomass burning
Photooxidation
Aqueous phase
Humic-like substances (HULIS)


SIRT1 Inhibits High Shear Stress-Induced Apoptosis in Rat Cortical Neurons.

Abstract:
Introduction
Sirtuin1 (SIRT1), one of NAD+-dependent protein deacetylases, is proved to be neuroprotective in aging diseases, but its effect on neuronal apoptosis has not been clarified. To investigate the role of SIRT1 in inhibiting neuronal apoptosis, SIRT1 was interfered or overexpressed in cortical neurons.

Methods
We exerted overloading laminar shear stress with 10 dyn/cm2 for 4, 8, and 12 h on neurons to cause cortical neuronal apoptosis, and the apoptosis percentage was tested by TUNEL assay. The adenovirus plasmids containing SIRT1 RNA interference or SIRT1 wild type gene were transfected into neurons before shear stress loading. SIRT1 mRNA and protein level were tested by Real-time PCR, immunofluorescence and western blots assay.

Results
SIRT1 was primarily expressed in nucleus of cortical neurons, and its mRNA level was significantly increased after 4 h stimulation. SIRT1 RNAi cortical neurons had higher TUNEL positive cells, while SIRT1 overexpression significantly decreased the percentage of died cells induced by shear stress compared to control group.

Conclusions
SIRT1 plays a neuroprotective role in shear stress induced apoptosis and could be as potential pharmacological targets against neuronal degeneration in future.

Song|Wei|W| Liu|Mei-Li|ML| Zhao|Zhi-Jun|ZJ| Huang|Chong-Quan|CQ| Xu|Jun-Wei|JW| Wang|An-Qing|AQ| Li|Ping|P| Fan|Yu-Bo|YB|

SIRT1
Apoptosis
Cortical neurons
Shear stress
Neuroprotective effect


Sensitization of endocrine organs to anterior pituitary hormones by the autonomic nervous system.

Abstract: Hormone secretion from endocrine glands constitutes a primary component of homeostatic control systems that defend whole body tissue viability and function. Endocrine organ secretion is controlled by efferent mechanisms that consist of both hormonal and neural elements. Anatomical evidence for dual control has led to increased understanding of how autonomic neural activity modulates functional sensitivity to hormonal input. The clinical relevance of autonomic-endocrine interactions is illustrated by examining functional control of the adrenal cortex and the ovary, two tissues that require tropic support from the anterior pituitary and receive sympathetic neural input. Extrapituitary mechanisms of adrenal cortical control including sympathetic neural activity have been implicated in controlling the amplitude of the cortisol awakening response (CAR), a diagnostic index of hypothalamic-pituitary-adrenal activity in humans. In addition, increases in sympathetic neural tone have been implicated in polycystic ovary syndrome (PCOS), a leading cause of female infertility. These examples offer strong evidence for the capability of autonomic neural activity to alter the functional sensitivity of endocrine glands. This interaction has significant clinical relevance and needs to be incorporated into our view in assessing endocrine organ function and dysfunction.

anterior pituitary
autonomic
adrenal cortex
ovary
sympathetic
cortisol awakening response
polycystic ovary syndrome
Autonomic–endocrine interaction


Light and scanning electron microscopy-based foliar micro morphological tools for the identification of fodder grass taxa.

Abstract: Fertile plain of Central Punjab Pakistan is rich with fodder grasses and from centuries the local inhabitants of this area have been using their regional grasses for ruminant feeding. However, they always faced difficulties in identification because of their overlapping vernacular names, more or less identical leaf shapes, indefinite variations in stem branching pattern, and reduced floral parts. Hence, the current study has provided a detailed and comprehensive micro-morphological analysis of 53 ethnobotanical fodder grass taxa. A variety of quantitative and qualitative leaf epidermal micromorphological traits was studied and results reported epidermal characters like stomatal index, silica bodies, prickles, microhairs, hook cells as most diagnostic in delimitation of species, and genera. As stomatal index was 79% in Poa annua while in its closely related species Poa infirmai was 85%. Similarly, Cenchrus ciliaris can be differentiated from Cenchrus pennisetiformis on the basis of silica body shape as butterfly shaped in former and dumbbell shaped in later one. Moreover, prickles were present in Chrysopogon aucheri while absent in Chrysopogon zizanioides. Hence, overall this study declared that diversity and variations in foliar micromorphological characters are valuable and supportive in the identification of grasses at the specific and generic level.

Central Punjab Pakistan
ethnobotanical fodder grass
leaf epidermal
leaf transvers sectioning
micro morphological characters


Patients Hospitalized with pH1N1 Influenza in an Academic Community Medical Center.

Abstract:
BACKGROUND
The emergence of a novel strain of pandemic influenza (pH1N1) in 2009 presented significant challenges to health care facilities worldwide. In our academic community medical center in suburban Philadelphia, we noted our first pH1N1 diagnosis in September 2009. We sought to assess the impact of pH1N1 disease on our hospitalized patient population.

METHODS
We prospectively collected clinical and epidemiological data on 29 consecutive patients that were admitted to our hospital with a primary or secondary diagnosis of influenza from October 1-November 30, 2009. Data were obtained through care of the patients and chart review.

RESULTS
Prominent symptoms on admission included fever, hypoxia, cough, myalgias, and diarrhea, with leukocytosis and neutrophilia. Pre-existing medical conditions included asthma, pregnancy, immunosuppressive therapy, and sickle cell disease. All but 5 of the patients were under 60 years of age. Three patients had culture-documented bacterial or mycoplasma infections. All but two of the patients received oseltamivir. Six required admission to the intensive care unit but only one patient died.

CONCLUSIONS
Our population of hospitalized patients with novel pH1N1 influenza demonstrated many of the features that have been associated with pH1N1 disease in other populations. Most of the patients were women and none of the patients died directly as a complication of influenza. We observed a cluster of patients with a tetrad of features comprising a history of asthma, obesity, female gender, and African-American race. Individuals with this constellation of factors should be specifically targeted for pH1N1 vaccination.

Bergman|Hagit|H|
Livornese|Lawrence L|LL|
Sambhara|Suryaprakash|S|
Santoro|Jerome|J|
Dessain|Scott K|SK|

pH1N1 Influenza
neutrophilia
immunosuppression
vaccination
PCR
RIDT.


Characterization of protein hydrolysates from blue whiting (Micromesistius poutassou) and their application in beverage fortification.

Abstract: Enzymatic hydrolysis of fish proteins has been employed as a principle method for converting under-utilised fish into valuable products for the pharmaceutical and health food industries. In this study, six commercial enzymes were tested for their ability to make fish protein hydrolysate powders from whole blue whiting. The chemical and functional properties of these powders were compared. The powders all had high solubility (>80%) across a wide pH range in water and their solubility improved further within a vitamin-tea beverage matrix (>85%). Varying degrees of anti-oxidant activities were recorded for the powders using three model systems (DPPH, ferrous chelating and reducing power). This study demonstrates that commercial enzymes are useful for the extraction and alteration of fish protein from a low value source to produce highly digestible, low molecular weight peptide powders that could be used as a fortifying health ingredient, especially in beverages.

Egerton|Sian|S|
Culloty|Sarah|S|
Whooley|Jason|J|
Stanton|Catherine|C|
Ross|R Paul|RP|

Fish protein hydrolysates
Functional properties
Anti-oxidant
Health ingredients
Amino acids


The demographic features and outcome indicators of the Barbados HIV Pre-exposure Prophylaxis Program, 2018-2019.

Abstract:
Objective
To assess the demographics, risk profiles and outcome indicators of one of the few government-supported programs on pre-exposure prophylaxis (PrEP) in the English-speaking Caribbean.

Methods
Chart review of all persons enrolled into the national PrEP Program from its inception on March 1st 2018 to November 30th 2019, with a descriptive summary analysis of the data extracted.

Results
Of the 134 persons enrolled into the program most identified as men who have sex with men (67.9%), followed by men who have sex with men and women (14.9%); there were 20 persons, mostly men (85%), in sero-discordant relationships. PrEP uptake was 96%; however, the continuation rate (continuing for three consecutive months after initiation) was 61.5%. Continuation status for many could not be ascertained due to loss-to-follow-up. PrEP-associated toxicity prevalence was 2.3%, although side-effects occurred in 52% (mostly gastrointestinal). HIV positivity during the study period was 1.5%.

Conclusions
Uptake of Barbados' national PrEP Program is excellent but fairly low continuation rates and the HIV positivity rate indicate the need for improved pre-ART initiation education and follow-up processes. Service utilisation is mainly by men who have sex with men, and provision expansion to other civil society partners and private practitioners, as well as increased public awareness could increase access by other high-risk groups.

Barbados
HIV
pre-exposure prophylaxis
Caribbean Region


Efficient pretreatment of industrial estate wastewater for biodegradability enhancement using a micro-electrolysis-circulatory system.

Abstract: A self-made micro-electrolysis-circulatory system with the mixture regime of an upflow bed and reactor was tested for the pretreatment of industrial estate wastewater with a low ratio of biological to chemical oxygen demand (BOD5/COD) at room temperature, 1:1 vol ratio of sponge iron (SFe)/granular activated carbon (GAC), and an intermittent process in aeration and discharge. The system efficiency was evaluated in view of the effects of various processes (hydraulic retention time (HRT), fillers/wastewater ratio (S/L) and aeration). COD reduction of about 51% was obtained for industrial estate wastewater at an S/L ratio of 25%, refluence rate of 16 L/h, HRT of 24 h, and aeration of 60 L/h as the optimal conditions. The considerable change in the calculated BOD5/COD ratio, from 0.07 to 0.49, showed favorable application of the micro-electrolysis-circulatory system for the reductive and oxidative degradation of organic pollutants to enhance wastewater biodegradability. The reusability of the SFe was also investigated after three successive runs. On the basis of the results of Fe leaching, HRT, S/L ratio, scanning electron microscopy observation, and X-ray photoelectron spectroscopic analysis, the corrosion products facilitated by the inherent porosity of SFe played a significant role due to different oxygen conditions in the surface and internal layers. One result from the removal of organic pollutants dominated by the galvanic cell reactions between SFe and GAC was observed, and the integration coagulation in the bulk solution was mainly attributed to the leaching of Fe. The innovative approach described in this study provides a promising and economical technology for pretreatment of industrial wastewater prior to a biological process.

Ma|Cong|C| Ran|Zhilin|Z| Yang|Zhiqing|Z| Wang|Liang|L| Wen|Chen|C| Zhao|Bing|B| Zhang|Hongwei|H|

D057919:Biological Oxygen Demand Analysis

Industrial estate wastewater
Biodegradability
Micro-electrolysis-circulatory system
Sponge iron
COD removal


Perceiving Linear-Velocity by Multiphoton Upconversion.

Abstract: Up to now, the rising edge of the upconversion process does not receive due attention. Herein, a demonstration utilizing the feature of the rising edge to practically detect the linear-velocity of an object is presented. Typically, upconversion processes with different numbers of participant photons would exhibit diversity in the rising edge. On this account, when the emitter is moving, the emission intensity ratio of different multiphoton processes will vary with changing linear-velocity, which enables accurate speed detection through spectral analysis. To illustrate this principle, in this work, the modeling and numerical simulation were first performed, and then experimental demonstration was carried out in which core-shell upconversion nanocrystals were elaborately designed and fabricated as the speed sensing probe to calibrate the speed of a homemade turnplate. It is believed that the present work will exploit a novel speed sensing method and find a new application for lanthanide-doped upconversion materials.

Upconversion
Fluoride nanocrystals
Lanthanide luminescent materials
Non-steady-state emission
Velocimetry


Peripheral Immune Cell Ratios and Clinical Outcomes in Seropositive Autoimmune Encephalitis: A Study by the Australian Autoimmune Encephalitis Consortium.

Abstract:
Objective
To examine the utility of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as biomarkers of prognosis in seropositive autoimmune encephalitis (AE).

Methods
In this multicenter study, we retrospectively analyzed 57 cases of seropositive AE with hospital admissions between January 2008 and June 2019. The initial full blood examination was used to determine each patients' NLR and MLR. The modified Rankin Scale (mRS) was utilized to assess the patients' follow-up disability at 12 months and then at final follow-up. Primary outcomes were mortality and mRS, while secondary outcomes were failure of first line treatment, ICU admission, and clinical relapse. Univariate and multivariable regression analysis was performed.

Results
During initial hospital admission 44.7% of patients had unsuccessful first line treatment. After a median follow-up of 700 days, 82.7% had good functional outcome (mRS ≤2) while five patients had died. On multivariable analysis, high NLR was associated with higher odds of first line treatment failure (OR 1.32, 95% CI 1.03-1.69, p = 0.029). Increased MLR was not associated with any short or long-term outcome.

Conclusions
NLR on initial hospital admission blood tests may be provide important prognostic information for cases of seropositive AE. This study demonstrates the potential use of NLR as a prognostic marker in the clinical evaluation of patients with seropositive AE.

Broadley|James|J|
Wesselingh|Robb|R|
Seneviratne|Udaya|U|
Kyndt|Chris|C|
Beech|Paul|P|
Buzzard|Katherine|K|
Nesbitt|Cassie|C|
D'Souza|Wendyl|W|
Brodtmann|Amy|A|
Kalincik|Tomas|T|
Butzkueven|Helmut|H|
O'Brien|Terence J|TJ|
Monif|Mastura|M|
|||

autoimmune encephalitis
neutrophil-to-lymphocyte ratio
monocyte-to-lymphocyte ratio
biomarker
prognosis


Gonadotrope Tumors.

Abstract: Gonadotrope tumors arise from the gonadotropes of the adenohypophysis. These cells rarely give rise to hyperplasia, usually only in the setting of long-standing premature gonadal failure. In contrast, gonadotrope tumors represent one of the most frequent types of pituitary tumors. Despite their relatively common occurrence, the pathogenesis of gonadotrope tumors remains unknown. Effective nonsurgical therapies remain out of reach. We review the pituitary gonadotrope from the morphologic and functional perspectives to better understand its involvement as the cell of origin of a frequent type of pituitary tumor.

gonadotrope tumor pathogenesis morphology adenoma biochemistry epidemiology immunohistochemistry


Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin.

Abstract:
BACKGROUND
Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT.

OBJECTIVES
To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[14C]PT was investigated.

METHOD
In vitro penetration of [14C]PT into and through excised human skin was measured following application of Zn[14C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum.

RESULTS
The steady-state flux and cumulative absorption of Zn[14C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[14C]PT and 3H2O absorption when dosed from both aqueous formulations, but not from castor oil.

CONCLUSION
These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [14C]PT kinetics, is controlled by particle dissolution and molecular speciation.

Rush|Allison K|AK|
Nash|J F|JF|
Smith Iii|Edward D|ED|
Kasting|Gerald B|GB|

Percutaneous absorption
Antimicrobial
Dissolution
In vitro skin penetration/permeation
Topical bioavailability


Community mobilisation to prevent violence against women and girls in eastern India through participatory learning and action with women's groups facilitated by accredited social health activists: a before-and-after pilot study.

Abstract:
BACKGROUND
Almost one in three married Indian women have ever experienced physical, sexual, or emotional violence from husbands in their lifetime. We aimed to investigate the preliminary effects of community mobilisation through participatory learning and action groups facilitated by Accredited Social Health Activists (ASHAs), coupled with access to counselling, to prevent violence against women and girls in Jharkhand, eastern India.

METHODS
We piloted a cycle of 16 participatory learning and action meetings with women's groups facilitated by ASHAs in rural Jharkhand. Participants identified common forms of violence against women and girls, prioritised the ones they wanted to address, developed locally feasible strategies to address them, implemented the strategies, and evaluated the process. We also trained two counsellors and two ASHA supervisors to support survivors, and gave ASHAs information about legal, health, and police services. We did a before-and-after pilot study involving baseline and endline surveys with group members to estimate preliminary effects of these activities on the acceptability of violence, prevalence of past year emotional and physical violence, and help-seeking.

RESULTS
ASHAs successfully conducted monthly participatory learning and action meetings with 39 women's groups in 22 villages of West Singhbhum district, Jharkhand, between June 2016 and September 2017. We interviewed 59% (679/1149) of women registered with groups at baseline, and 63% (861/1371) at endline. More women reported that violence was unacceptable in all seven scenarios presented to them at endline compared to baseline (adjusted Odds Ratio [aOR]: 1.87, 95%: 1.39-2.52). Fewer women reported experiencing emotional violence from their husbands in the last 12 months (aOR: 0.55, 95% CI: 0.43-0.71), and more sought help if it occurred (aOR: 2.19, 95% CI: 1.51-3.17). In addition, fewer women reported experiencing emotional or physical violence from family members other than their husbands in the last 12 months (aOR: 0.41, 95% CI: 0.32-0.53, and aOR: 0.36, 95% CI: 0.26-0.50, respectively).

CONCLUSION
Combining participatory learning and action meetings facilitated by ASHAs with access to counselling was an acceptable strategy to address violence against women and girls in rural communities of Jharkhand. The approach warrants further implementation and evaluation as part of a comprehensive response to violence.

Nair|Nirmala|N|
Daruwalla|Nayreen|N|
Osrin|David|D|
Rath|Suchitra|S|
Gagrai|Sumitra|S|
Sahu|Rebati|R|
Pradhan|Hemanta|H|
De|Megha|M|
Ambavkar|Gauri|G|
Das|Nibha|N|
Dungdung|G Pramila|GP|
Mohan|Damini|D|
Munda|Bahadur|B|
Singh|Vijay|V|
Tripathy|Prasanta|P|
Prost|Audrey|A|

Community mobilisation
Violence against women and girls
India
Participatory learning and action
Indigenous communities


Expression Patterns, Genomic Conservation and Input Into Developmental Regulation of the GGDEF/EAL/HD-GYP Domain Proteins in Streptomyces.

Abstract: To proliferate, antibiotic-producing Streptomyces undergo a complex developmental transition from vegetative growth to the production of aerial hyphae and spores. This morphological switch is controlled by the signaling molecule cyclic bis-(3',5') di-guanosine-mono-phosphate (c-di-GMP) that binds to the master developmental regulator, BldD, leading to repression of key sporulation genes during vegetative growth. However, a systematical analysis of all the GGDEF/EAL/HD-GYP proteins that control c-di-GMP levels in Streptomyces is still lacking. Here, we have FLAG-tagged all 10 c-di-GMP turnover proteins in Streptomyces venezuelae and characterized their expression patterns throughout the life cycle, revealing that the diguanylate cyclase (DGC) CdgB and the phosphodiesterase (PDE) RmdB are the most abundant GGDEF/EAL proteins. Moreover, we have deleted all the genes coding for c-di-GMP turnover enzymes individually and analyzed morphogenesis of the mutants in macrocolonies. We show that the composite GGDEF-EAL protein CdgC is an active DGC and that deletion of the DGCs cdgB and cdgC enhance sporulation whereas deletion of the PDEs rmdA and rmdB delay development in S. venezuelae. By comparing the pan genome of 93 fully sequenced Streptomyces species we show that the DGCs CdgA, CdgB, and CdgC, and the PDE RmdB represent the most conserved c-di-GMP-signaling proteins in the genus Streptomyces.

Al-Bassam|Mahmoud M|MM|
Haist|Julian|J|
Neumann|Sara Alina|SA|
Lindenberg|Sandra|S|
Tschowri|Natalia|N|

GGDEF EAL HD-GYP Streptomyces c-di-GMP development


Deletion of the receptor tyrosine kinase Tyro3 inhibits synovial hyperplasia and bone damage in arthritis.

Abstract:
OBJECTIVE
To test whether the tyrosine kinase Tyro3 affects arthritis. Tyro3, the ligand of growth arrest-specific protein 6 (GAS6) is a receptor tyrosine kinase involved in cell survival. Tyro3 and GAS6 are expressed in the arthritic synovium, and in vitro studies have shown their role in osteoclast differentiation.

METHODS
Bone was assessed by micro CT and histomorphometry in Tyro3-deficient (Tyro3(-/-)) and wild-type mice. Arthritis was induced in both genotypes, and Gas6 level was measured by ELISA. Synovitis, synovial hyperplasia, bone erosion, osteoclast activation and osteoclast gene expression were assessed by histomorphometry and reverse transcriptase-PCR, respectively. In vitro osteoclast differentiation assays were performed in Tyro3(-/-) and wild-type mice. Furthermore, effects of Tyro3 and GAS6 on human synovial fibroblast proliferation and osteoclastogenesis were assessed in human cells.

RESULTS
Tyro3(-/-) mice had significantly higher bone mass than wild-type littermates. Induction of arthritis increased GAS6 serum levels. Arthritic Tyro3(-/-) mice showed less synovial hyperplasia, osteoclast numbers and bone damage compared with controls. In vivo expression of osteoclast-associated receptor and receptor activator of nuclear factor-κB and in vitro osteoclastogenesis were impaired in Tyro3(-/-) mice. GAS6 also induced synovial fibroblast proliferation and osteoclast differentiation in human cells in Tyro3-dependent manner.

CONCLUSIONS
These findings indicate that Tyro3 is a critical signal for synovial hyperplasia, osteoclast differentiation and bone erosion during arthritis. GAS6 and Tyro3 therefore constitute therapeutic targets to inhibit synovial hyperplasia and associated bone erosion.

Ruiz-Heiland|Gisela|G| Zhao|Yi|Y| Derer|Anja|A| Braun|Tobias|T| Engelke|Klaus|K| Neumann|Elena|E| Mueller-Ladner|Ulf|U| Liu|Yi|Y| Zwerina|Jochen|J| Schett|Georg|G|

D036341:Intercellular Signaling Peptides and Proteins

Arthritis
Synovitis
Rheumatoid Arthritis


Haplosporosomes, sporoplasmosomes and their putative taxonomic relationships in rhizarians and myxozoans.

Abstract: This paper reviews current knowledge of the structure, genesis, cytochemistry and putative functions of the haplosporosomes of haplosporidians (Urosporidium, Haplosporidium, Bonamia, Minchinia) and paramyxids (Paramyxa, Paramyxoides, Marteilia, Marteilioides, Paramarteilia), and the sporoplasmosomes of myxozoans (Myxozoa - Malacosporea, Myxosporea). In all 3 groups, these bodies occur in plasmodial trophic stages, disappear at the onset of sporogony, and reappear in the spore. Some haplosporidian haplosporosomes lack the internal membrane regarded as characteristic of these bodies and that phylum. Haplosporidian haplosporogenesis is through the Golgi (spherulosome in the spore), either to form haplosporosomes at the trans-Golgi network, or for the Golgi to produce formative bodies from which membranous vesicles bud, thus acquiring the external membrane. The former method also forms sporoplasmosomes in malacosporeans, while the latter is the common method of haplosporogenesis in paramyxids. Sporoplasmogenesis in myxosporeans is largely unknown. The haplosporosomes of Haplosporidium nelsoni and sporoplasmosomes of malacosporeans are similar in arraying themselves beneath the plasmodial plasma membrane with their internal membranes pointing to the exterior, possibly to secrete their contents to lyse host cells or repel haemocytes. It is concluded that these bodies are probably multifunctional within and between groups, their internal membranes separating different functional compartments, and their origin may be from common ancestors in the Neoproterozoic.

Hine|P M|PM|
Morris|D J|DJ|
Azevedo|C|C|
Feist|S W|SW|
Casal|G|G|0000-0002-9680-661X

haplosporosomes
sporoplasmosomes
taxonomic relationships
myxozoans
Functions
haplosporidians
paramyxids
ultrastructure


Bio-barcode technology for detection of Staphylococcus aureus protein A based on gold and iron nanoparticles.

Abstract: S. aureus is one of important causes of disease, food poisoning in humans and animals. The generally methods for detection of S. aureus is time consuming. Therefore, a new method is necessary for rapid, sensitive and specific diagnosis of S. aureus. In the present study, two probes and a Bio-barcode DNA were designed for detection of S. aureus (Protein A). Firstly, magnetic nanoparticle (MNPs) and gold nanoparticle (AuNPs) were synthesized at 80 °C and 100 °C, respectively. The AuNPs and the MNPs were functionalized with probe1, Bio-barcode DNA and probe2, respectively. Target DNA was added into the nanomaterial's system containing bio-barcode DNA-AuNPs-probe1 and probe2-MNPs to formed bio-barcode DNA-AuNPs-probe1-target DNA-probe2-MNPs complex. The bio-barcode DNA-AuNPs-probe1-target DNA-probe2-MNPs complex was separated with magnetic field. Finally, the bio-barcode DNA was released from surface of complex using DTT (0.8 M) and there was isolated of nanoparticles by magnetic field and centrifuge. The fluorescence intensity of bio-barcode DNA was measured in different concentrations of S. aureus (101 to 108 CFU mL-1) by fluorescence spectrophotometry. The results showed that standard curve was linearly from 102 to 107 CFU mL-1. Limit of detection of bio-barcode assay for both PBS and real samples was 86 CFU mL-1.

Amini|Ali|A| Kamali|Mehdi|M| Amini|Bahram|B| Najafi|Azam|A| Narmani|Asghar|A| Hasani|Leila|L| Rashidiani|Jamal|J| Kooshki|Hamid|H| Elahi|Narges|N|

D015373:Bacterial Typing Techniques
D015374:Biosensing Techniques
D058893:DNA Barcoding, Taxonomic
D015342:DNA Probes
D004269:DNA, Bacterial
D006046:Gold
D006801:Humans
D007501:Iron
D057230:Limit of Detection
D059346:Magnets
D053768:Metal Nanoparticles
D013050:Spectrometry, Fluorescence
D013205:Staphylococcal Protein A
D013211:Staphylococcus aureus


Clotting during autologous hematopoietic progenitor cells collection.

Abstract: Autologous hematopoietic progenitor cell (HPC) transplant through peripheral blood mobilization and leukapheresis is a standard treatment for many patients with hematopoietic malignancies. Although leukapheresis is usually completed with no complications, we present a case in which the hematopoietic progenitor cells clotted during collection. The patient had no history of hypercoagulopathy. It was identified that the anticoagulant infusion line was partially constricted by a blood warmer clamp. The machine did not alarm. Most of the multiple Food and Drug Administration reports of clotting occurring during apheresis procedures were due to the patients' preexisting hypercoagulopathy or insufficient anticoagulant solution being used. The machine alarmed in most of these cases. Our case demonstrates that inadequate anticoagulation can occur during an HPC collection procedure without activation of an alarm.

D018380:Hematopoietic Stem Cell Transplantation

clotting
hematopoietic progenitor cells
collection
anticoagulants
apheresis


MicroRNA-17-92 cluster regulates pancreatic beta-cell proliferation and adaptation.

Abstract: MiR-17-92 cluster contributes to the regulation of mammalian development, aging and tumorigenesis. The functional roles of miR-17-92 in pancreatic beta-cells are largely unknown. In this study, we found that conditional deletion of miR-17-92 in mouse pancreatic beta-cells (miR-17-92βKO) significantly reduces glucose tolerance and the first phase of insulin secretion, despite normal ad libitum fed and fasting glucose levels. Proliferation is down-regulated in pancreatic beta-cells after deleting miR-17-92. MiR-17-92βKO mice show higher phosphatase and tensin homologue (PTEN) and lower phosphorylated AKT in islets. Under high fat diet challenge for 16 weeks, miR-17-92βKO mice lose compensation and exhibit higher glucose levels, and lower insulin secretion. Collectively, these data suggest that miR-17-92 is a critical contributor to molecular mechanisms regulating glucose-stimulated insulin secretion and pancreatic beta-cell adaptation under metabolic stress.

Chen|Yaxi|Y|
Tian|Li|L|
Wan|Shan|S|
Xie|Ying|Y|
Chen|Xiang|X|
Ji|Xiao|X|
Zhao|Qian|Q|
Wang|Chunyu|C|
Zhang|Kun|K|
Hock|Janet M|JM|
Tian|Haoming|H|
Yu|Xijie|X|

Pancreatic beta-cells
Proliferation
Adaptation
MiR-17-92
PTEN


Experimental and theoretical spectroscopic analysis, HOMO-LUMO, and NBO studies of cyanuric chloride.

Abstract: The vibrational spectral analysis of cyanuric chloride was carried out by using FT-Raman and FT-IR spectra in the range 100-4000cm(-1) and 400-4000cm(-1) respectively. The structure optimization was done and structural characteristics were determined by Density Functional Theory (B3LYP) method with 6-31G(d,p) and 6-311++G(d,p) basis sets. The vibrational wavenumbers have been calculated and scaled values are compared with experimental FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of the molecule has been made on the basis of the calculated Potential Energy Distribution (PED). The Natural bonding orbital (NBO) analysis performed to confirm the stability of the molecule arising from hyper conjugation and delocalization. The Mulliken atomic charges were also calculated. The computed HOMO-LUMO energy gap shows that charge transfer occurs within the molecule. The thermodynamic properties at different temperatures have been calculated from the vibrational analysis.

Prabhaharan|M|M|
Prabakaran|A R|AR|
Srinivasan|S|S|
Gunasekaran|S|S|

D017550:Spectroscopy, Fourier Transform Infrared


Coupled changes of bacterial community and function in the gut of mud crab (Scylla Paramamosain) in response to Baimang disease.

Abstract: Increasing evidence has revealed a close association between intestinal bacterial community and hosts health. However, it is unclear whether and what extend Baimang disease alters the intestinal microbiota in mud crab (Scylla paramamosain). Here, we conducted intestinal contents Illumina sequencing of healthy and Baimang diseased mud crab (S. paramamosain) to understand bacterial community variations among health status. In addition, bacterial functional predication was used to investigate whether and how the bacteria variations further change their functions? The phyla of Proteobacteria, Fusobacteria, Cyanobacteria, Tenericutes, Firmicutes, Bacteroidetes, and Spirochaetae constituted over 96.44% of the total intestinal bacteria, with being the dominant taxa. The 7 most significantly different orders, including the increased four orders of Clostridiales, Entomoplasmatales, Bacteroidales, and Mycoplasmatales and the decreased three orders of Vibrionales, Campylobacterales, and Fusobacteriales, accounted for 61.14% dissimilarity, probably being the indicator taxa of Baimang disease. Accordingly, 12 Kyoto Encyclopedia of Genes and Genomes orthologies in level 3 shifted significantly at the diseased crabs. Especially, bacterial secretion system, secretion system, lipopolysaccharide biosynthesis proteins and Vibrio cholerae pathogenic cycle, being related to bacterial virulence, were reduced. In addition, the reduced butanoate metabolism, and induced methane metabolism and one carbon pool by folate were important metabolic processes of probiotic, such as Bacteroides spp. and Clostridium spp., with playing critical roles in host health. This study suggests that Baimang disease coupled altered the intestinal bacterial communities and functions, providing timely information for further analysis the influencing mechanism of Baimang disease in mud crab (S. paramamosain).

Scylla paramamosain
Baimang disease
Intestinal bacterial community
Bacterial function


Vitamin D metabolism in dogs with and without hypercalciuric calcium oxalate urolithiasis.

Abstract:
BACKGROUND
There are abnormalities in vitamin D metabolism in people with calcium nephrolithiasis, but limited data are available on vitamin D status in dogs with calcium oxalate (CaOx) urolithiasis.

OBJECTIVE
To compare serum concentrations of vitamin D metabolites in dogs with and without hypercalciuric CaOx urolithiasis.

ANIMALS
Thirty-eight dogs with (n = 19) and without (n = 19) a history of CaOx urolithiasis and hypercalciuria.

METHODS
Retrospective cross-sectional study. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D] were measured. The ratios of 25(OH)D/24,25(OH)2 D and 1,25(OH)2 D/25(OH)D were compared between cases and controls.

RESULTS
There were no significant differences between cases and controls when comparing 25(OH)D, 24,25(OH)2 D, 1,25(OH)2 D, or 1,25(OH)2 D/25(OH)D. Cases had higher 25(OH)D/24,25(OH)2 D (median = 1.40, range = 0.98-1.58) compared to controls (median = 1.16, range = 0.92-2.75; P = .01). There was overlap in the ranges for 25(OH)D/24,25(OH)2 D between cases and controls, but 6 cases (32%) had ratios above the control dog range. There was a moderate positive correlation between the ratio of 25(OH)D/24,25(OH)2 D and urinary calcium-to-creatinine ratios (r = 0.40, 95% confidence interval = 0.10-0.64; P = .01).

CONCLUSIONS AND CLINICAL IMPORTANCE
These data suggest that decreased conversion of 25(OH)D to 24,25(OH)2 D occurs in a subset of dogs with CaOx urolithiasis. Abnormalities in vitamin D metabolism might contribute to stone risk in dogs.


Nuclear import factor transportin and arginine methyltransferase 1 modify FUS neurotoxicity in Drosophila.

Abstract: Inclusions containing Fused in Sarcoma (FUS) are found in familial and sporadic cases of the incurable progressive motor neuron disease amyotrophic lateral sclerosis and in a common form of dementia, frontotemporal dementia. Most disease-associated mutations are located in the C-terminal proline-tyrosine nuclear localization sequence (PY-NLS) of FUS and impair its nuclear import. It has been shown in cell culture that the nuclear import of FUS is mediated by transportin, which binds the PY-NLS and the last arginine/glycine/glycine-rich (RGG) domain of FUS. Methylation of this last RGG domain by protein arginine methyltransferases (PRMTs) weakens transportin binding and therefore impairs nuclear translocation of FUS. To investigate the requirements for the nuclear import of FUS in an in vivo model, we generated different transgenic Drosophila lines expressing human FUS wild type (hFUS wt) and two disease-related variants P525L and R495X, in which the NLS is mutated or completely absent, respectively. To rule out effects caused by heterologous hFUS expression, we analysed the corresponding variants for the Drosophila FUS orthologue Cabeza (Caz wt, P398L, Q349X). Expression of these variants in eyes and motor neurons confirmed the PY-NLS-dependent nuclear localization of FUS/Caz and caused neurodegenerative effects. Surprisingly, FUS/Caz toxicity was correlated to the degree of its nuclear localization in this overexpression model. High levels of nuclear FUS/Caz became insoluble and reduced the endogenous Caz levels, confirming FUS autoregulation in Drosophila. RNAi-mediated knockdown of the two transportin orthologues interfered with the nuclear import of FUS/Caz and also enhanced the eye phenotype. Finally, we screened the Drosophila PRMT proteins (DART1-9) and found that knockdown of Dart1 led to a reduction in methylation of hFUS P525L and aggravated its phenotype. These findings show that the molecular mechanisms controlling the nuclear import of FUS/Caz and FUS autoregulation are conserved between humans and Drosophila. In addition to the well-known neurodegenerative effects of FUS loss-of function, our data suggest toxic potential of overexpressed FUS in the nucleus and of insoluble FUS.

Jäckel|Sandra|S|
Summerer|Anna K|AK|
Thömmes|Catherine M|CM|
Pan|Xia|X|
Voigt|Aaron|A|
Schulz|Jörg B|JB|
Rasse|Tobias M|TM|
Dormann|Dorothee|D|
Haass|Christian|C|
Kahle|Philipp J|PJ|

D021581:Active Transport, Cell Nucleus
D000818:Animals
D030801:Animals, Genetically Modified
D019175:DNA Methylation
D004195:Disease Models, Animal
D029721:Drosophila Proteins
D004331:Drosophila melanogaster
D005123:Eye
D055785:Gene Knockdown Techniques
D006801:Humans
D028884:Karyopherins
D008780:Methyltransferases
D009046:Motor Neurons
D009069:Movement Disorders
D009154:Mutation
D019636:Neurodegenerative Diseases
D034622:RNA Interference
D034702:RNA-Binding Protein FUS
D016601:RNA-Binding Proteins
D035362:Transcription Factor TFIID

Transportin FUS Drosophila PRMT Caz ALS FTLD


Prevention of pulmonary fibrosis with salvianolic acid a by inducing fibroblast cell cycle arrest and promoting apoptosis.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine (TCM), often in combination with other herbs, to treat a diversity of ailments. More recent studies have focused on its possible roles in the treatment of respiratory diseases (pneumonia and pulmonary fibrosis) and found that it has pharmacological activity that protects pulmonary morphology and function. However, the mechanism underlying this activity has not yet been clarified.

MATERIALS AND METHODS
The purpose of this study was to investigate the anti-pulmonary fibrosis effects exerted by salvianolic acid A (SAA), the ingredient responsible for the pharmacological activity of Danshen, and the underlying mechanisms. Bleomycin (BLM)-induced rat pulmonary fibrosis was used to evaluate the antifibrotic role of SAA, and fibroblast cells were used to study the mechanism involved.

RESULTS
BLM-treated rats exhibited increased alveolar wall thickness and collagen deposition in lung tissues, but these pathologies were greatly attenuated by daily administration of SAA. We also found that SAA significantly inhibited the proliferation, adhesion and migration of fibroblasts in vitro. This was partly due to a strong induction of cell cycle arrest and apoptosis upon SAA treatment. Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclin D1, cyclin E1, and cyclin B1, and increased expression of p53 and p21 in SAA-treated cells. In addition, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while cleaved caspase-3 protein increased upon SAA treatment.

CONCLUSIONS
These results suggest that the alleviation of rat pulmonary fibrosis by SAA is due to the inhibition of fibroblast proliferation and induction of apoptosis, which occurs mainly through p53-dependent growth arrest and apoptosis. We suggest that SAA should be considered as a potential novel therapeutic agent for the treatment of fibrotic lung diseases.

Pan|Yongming|Y| Fu|Huiying|H| Kong|Qing|Q| Xiao|Yin|Y| Shou|Qiyang|Q| Chen|Hongqiang|H| Ke|Yuehai|Y| Chen|Minli|M|

Pulmonary fibrosis
Salvianolic acid A
Cell cycle
Apoptosis
Phenotypic modulation


Pancreatic and Hepatic Metastasis of an Undiagnosed Choriocarcinoma: An Exceptional Cause of Haemoperitoneum in Young Women - Report of a Rare Case.

Abstract: Haemoperitoneum in women of reproductive age usually suggests either ruptured ectopic pregnancy or ruptured ovarian cysts. Metastatic choriocarcinoma is considered the least common cause of haemoperitoneum in women of childbearing age. We report a rare case of pancreatic and hepatic metastasis of choriocarcinoma in a young, 30-year-old female who had delivered 10 months prior at term gestation with no previous history of gestational trophoblastic disease or molar pregnancy. She had a short history of fever and pain in the right hypochondrium, with findings of hypovolaemic shock due to intraperitoneal haemorrhage. Unfortunately, the patient expired with massive uncontrolled bleeding from liver metastasis despite 2 emergency laparotomies within 12 h. This case report is an apt reminder to clinicians to include metastatic choriocarcinoma on the list of differential diagnoses for haemoperitoneum with a positive pregnancy test in women of reproductive age to diagnose early and to avoid life-threatening consequences.

Fatema|Nishat|N|
Arora|Neeru Vinod|NV|
Al Abri|Fatma Majid|FM|
Khan|Yaseer Muhammad Tareq|YM|


The oldest fossil darkling beetle of the genus Neomida Latreille, 1829 (Coleoptera: Tenebrionidae) from Eocene Baltic amber examined with X-ray microtomography.

Abstract: Based on a single well-preserved specimen from Eocene Baltic amber, a new tenebrionid beetle Neomida groehni Nabozhenko et Bukejs sp. nov. (Diaperinae: Diaperini) is described and illustrated using phase-contrast X-ray microtomography. This oldest representative of the genus differs from all known extant and extinct congeners by the dorsally very weakly convex pronotum with undulate lateral margins (while other Neomida have a pronotum that is strongly convex along its transverse axis, with evenly rounded lateral margins); distinct, right posterior angles of pronotum; and elevated sutural area of the elytra.

Nabozhenko|Maxim V|MV|
KairiŠs|Kristaps|K|
Bukejs|Andris|A|

Coleoptera, Diaperinae, palaeontology, new species, Cenozoic, fossil resin, X-ray micro-CT


Static Regulation and Dynamic Evolution of Single-Atom Catalysts in Thermal Catalytic Reactions.

Abstract: Single-atom catalysts provide an ideal platform to bridge the gap between homogenous and heterogeneous catalysts. Here, the recent progress in this field is reported from the perspectives of static regulation and dynamic evolution. The syntheses and characterizations of single-atom catalysts are briefly discussed as a prerequisite for catalytic investigation. From the perspective of static regulation, the metal-support interaction is illustrated in how the supports alter the electronic properties of single atoms and how the single atoms activate the inert atoms in supports. The synergy between single atoms is highlighted. Besides these static views, the surface reconstruction, such as displacement and aggregation of single atoms in catalytic conditions, is summarized. Finally, the current technical challenges and mechanistic debates in single-atom heterogeneous catalysts are discussed.

static regulation
dynamic evolution
thermal catalytic reactions
single‐atom catalysts


Stencil Micropatterning for Spatial Control of Human Pluripotent Stem Cell Fate Heterogeneity.

Abstract: Human pluripotent stem cells (hPSCs) have the intrinsic ability to differentiate and self-organize into distinct tissue patterns, although this requires the presentation of spatial environmental cues, i.e., biochemical and mechanical gradients. Cell micropatterning technologies potentially offer the means to spatially control stem cell microenvironments and organize the resultant differentiation fates. Here, we describe stencil micropatterning as a simple and robust method to generate hPSC micropatterns for controlling hPSC differentiation patterns. hPSC micropatterns are specified by the geometries of the cell stencil through-holes, which physically confine the locations where the underlying extracellular matrix and hPSCs can access and attach to the substrate. This confers the unique capability of stencil micropatterning to work with a variety of culture substrates and extracellular matrices for optimal hPSC culture. We present the detailed steps of stencil micropatterning to successfully generate hPSC micropatterns, which can be used to investigate how spatial polarization of cell adhesion results in cell fate heterogeneity.

D002448:Cell Adhesion
D018929:Cell Culture Techniques
D002454:Cell Differentiation
D005109:Extracellular Matrix
D006801:Humans
D039904:Pluripotent Stem Cells
D055153:Stem Cell Niche

Stencil
Human pluripotent stem cells
Tissue patterning
Cell micropatterning
Differentiation fate
Embryonic development
Spatial organization


Modeling Predictive Age-Dependent and Age-Independent Symptoms and Comorbidities of Patients Seeking Treatment for COVID-19: Model Development and Validation Study.

Abstract:
BACKGROUND
The COVID-19 pandemic continues to ravage and burden hospitals around the world. The epidemic started in Wuhan, China, and was subsequently recognized by the World Health Organization as an international public health emergency and declared a pandemic in March 2020. Since then, the disruptions caused by the COVID-19 pandemic have had an unparalleled effect on all aspects of life.

OBJECTIVE
With increasing total hospitalization and intensive care unit admissions, a better understanding of features related to patients with COVID-19 could help health care workers stratify patients based on the risk of developing a more severe case of COVID-19. Using predictive models, we strive to select the features that are most associated with more severe cases of COVID-19.

METHODS
Over 3 million participants reported their potential symptoms of COVID-19, along with their comorbidities and demographic information, on a smartphone-based app. Using data from the >10,000 individuals who indicated that they had tested positive for COVID-19 in the United Kingdom, we leveraged the Elastic Net regularized binary classifier to derive the predictors that are most correlated with users having a severe enough case of COVID-19 to seek treatment in a hospital setting. We then analyzed such features in relation to age and other demographics and their longitudinal trend.

RESULTS
The most predictive features found include fever, use of immunosuppressant medication, use of a mobility aid, shortness of breath, and severe fatigue. Such features are age-related, and some are disproportionally high in minority populations.

CONCLUSIONS
Predictors selected from the predictive models can be used to stratify patients into groups based on how much medical attention they are expected to require. This could help health care workers devote valuable resources to prevent the escalation of the disease in vulnerable populations.

model
prediction
symptom
COVID-19
hospital
predictive modeling
app
age
clinical informatics
informatics
morbidity


Preventive Effect of Lactobacillus acidophilus XY27 on DSS-Induced Ulcerative Colitis in Mice.

Abstract:
Introduction
Lactobacillus acidophilus is widely used as probiotic supplement in functional foods due to its beneficial regulatory effects on host, such as immune regulation, anti-inflammatory, and antioxidant activities.

Aim
This study aimed to determine the preventive effect of Lactobacillus acidophilus XY27 (L. acidophilus XY27) on colitis induced by dextran sodium.

Methods
The mice were randomly divided into five groups. Except for the control group, the other four groups were induced for ulcerative colitis (UC) with dextran sodium sulfate (DSS), and three groups in DSS-groups were treated with L. acidophilus XY27, L. bulgaricus, and salicylazosulfapyridine. The weight change, DAI score, colon length, and length to weight ratio were tested. The oxidation index and the levels of inflammatory cytokines in the serum were measured. Subsequently, the gene expression levels of inflammatory factors in the colon tissue were determined by the Real-Time quantitative polymerase chain reaction (qRT-PCR) method.

Results
The results showed that the mice in the L. acidophilus XY27 group performed better in terms of weight, DAI score, colon length, and length to weight ratio or colonic pathological sections compared with the DSS-induced group. Further, the levels of tumor necrosis factor α (TNF-α), Interleukin-6 (IL-6), Interleukin-12 (IL-12) and Interleukin-1β (IL-1β), malondialdehyde (MDA) content, and myeloperoxidase activity in the serum of UC mice treated with L. acidophilus XY27 significantly decreased, while the levels of Interferon-γ (IFN-γ), Interleukin-10 (IL-10), Catalase (CAT), and total superoxide dismutase (SOD) significantly increased. The gene expression levels of Ets-like transcription factor-1 (EIK-1), IL-12, IL-1β, Cyclooxygenase 2 (COX-2), TNF-α, Escherichia coli, Lipopolysaccharide (LPS), and p100 in the colon significantly decreased while those of tight junction protein 1 (ZO-1), nuclear factor kappa B (NF-kB), p53, and NF-kappa-B inhibitor alpha (IκB-α) increased in the L. acidophilus XY27 group.

Conclusion
The results of the experiment suggested that L. acidophilus XY27 prevented colitis and alleviated symptoms in mice with DSS-induced UC, and also repaired the intestinal barrier function.

Lactobacillus acidophilus XY27
ulcerative colitis
dextran sodium sulfate
Lactobacillus bulgaricus


Metabolic syndrome and chronic kidney disease: Current status and future directions.

Abstract: Metabolic syndrome (MetS) is a term used to denote a combination of selected, widely prevalent cardiovascular disease (CVD)-related risk factors. Despite the ambiguous definition of MetS, it has been clearly associated with chronic kidney disease markers including reduced glomerular filtration rate, proteinuria and/or microalbuminuria, and histopathological markers such as tubular atrophy and interstitial fibrosis. However, the etiological role of MetS in chronic kidney disease (CKD) is less clear. The relationship between MetS and CKD is complex and bidirectional, and so is best understood when CKD is viewed as a common progressive illness along the course of which MetS, another common disease, may intervene and contribute. Possible mechanisms of renal injury include insulin resistance and oxidative stress, increased proinflammatory cytokine production, increased connective tissue growth and profibrotic factor production, increased microvascular injury, and renal ischemia. MetS also portends a higher CVD risk at all stages of CKD from early renal insufficiency to end-stage renal disease. Clinical interventions for MetS in the presence of CKD should include a combination of weight reduction, appropriate dietary modification and increase physical activity, plus targeting of individual CVD-related risk factors such as dysglycemia, hypertension, and dyslipidemia while conforming to relevant national societal guidelines.

Metabolic syndrome
Cardiovascular disease
Microalbuminuria
Progression
Hypertension
Diabetes
Dialysis
Hyperlipidemia
Obesity


Bilateral Tessier's 7 Cleft with Maxillary Duplication.

Abstract: Tessier's 7 cleft or lateral facial cleft are unusual lesions that result from failure of the embryonic mandibular and maxillary process of the first branchial arch to fuse properly and form the corners of the mouth. It may be seen alone or in combination with other anomalies, accompanied by varying degrees of severity. We report an extremely rare case of bilateral Tessier's 7 cleft along with maxillary duplication, macrostomia, bilateral posterior maxillary cleft, and mandibular retrusion in an 18-year-old male patient.

Macrostomia
Maxillary cleft
Tessier’s 7 cleft


Gender differences in the effect of diabetes mellitus and its treatment on osteoarthritic pain.

Abstract:
Objective
(1) To investigate differences in pain severity and its distribution between patients with and without diabetes mellitus (DM) in a population with advanced osteoarthritis (OA). (2) To explore the role of medication used for diabetes in these associations.

Research design and methods
This is a hospital-based cohort study of patients with advanced OA requiring total joint arthroplasty. Interviews and electronic records included: age, gender, occupation, DM (including medication and duration), analgesics used, anthropometry, joints affected by pain and disease duration. Joint pain was scored by the patients using numerical rating scale. Pain severity score was calculated by adding the number of joints affected by pain and the maximum pain score. All analyses were adjusted and/or stratified by gender, age and body mass index.

Results
In total, 489 patients with painful OA were included. From those, 139 patients had DM (30% males and 28% females, p=0.03). Pain severity, principally the number of joints affected by pain, and analgesic consumption, was higher in males with diabetes compared with males without diabetes (p=0.012 and OR=3.03; 95% CI 1.24 to 7.36, p=0.015, respectively). These associations were not significant in females (p=0.41 and p=0.66). Pain was more severe in males using insulin versus those who did not (p=0.025). Male subjects with diabetes had higher odds of hand pain or knee and hand pain compared with males without diabetes (OR=3.7, 95% CI 1.15 to 12; p=0.028 and OR=5.54; 95% CI 1.43 to 21.5, p=0.013, respectively).

Conclusions
Males with diabetes, especially those who require insulin, have more severe joint pain and consume more analgesics than males without diabetes or those who have DM and use other DM medication.

D000368:Aged
D018771:Arthralgia
D015331:Cohort Studies
D003924:Diabetes Mellitus, Type 2
D005260:Female
D006621:Hip Joint
D006801:Humans
D007004:Hypoglycemic Agents
D007719:Knee Joint
D008297:Male
D008875:Middle Aged
D020370:Osteoarthritis, Knee
D010147:Pain Measurement
D012307:Risk Factors
D012720:Severity of Illness Index
D012727:Sex Characteristics
D012737:Sex Factors

pain
adult diabetes
rheumatologic/musculoskeletal disease
risk factors


Risk of female breast cancer and serum concentrations of organochlorine pesticides and polychlorinated biphenyls: a case-control study in Tunisia.

Abstract: The aim of this study was to investigate the association between serum concentrations of a group of organochlorine pesticides/polychlorinated biphenyls with xenoestrogenic potential and the risk of breast cancer in a female population from Tunisia. The relationship between serum levels of the pollutants and the risk of cancer was assessed using logistic regression analyses. In the unadjusted models, β-hexachlorocyclohexane (β-HCH), hexachlorobenzene, heptachlor, polychlorinated biphenyl congeners 138, 153, and 180, and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with breast cancer risk. However, when the models were further adjusted for the selected covariates, only β-HCH and p,p'-DDE remained statistically significant, and heptachlor was borderline significant. In addition, analyses using POP concentration tertiles corroborated a positive dose-response relationship that was significant for p,p'-DDE (p-trend=0.020) and borderline significant for heptachlor (p-trend=0.078). A similar trend was also confirmed for β-HCH, in which concentrations≥limit of detection were positively associated with breast cancer risk (vs. concentrations<limit of detection, OR=3.44, p<0.05). Finally, the relative influence of each chemical in the presence of the others was assessed by entering the three chemicals in a single model with all covariates, and only β-HCH remained positively associated with the risk of cancer (OR:1.18, 95%CI: 1.05-1.34). Our findings suggest a potential association between exposure to at least one organochlorine pesticide and breast cancer risk. However, our results should be interpreted with caution, and further research is warranted to confirm these findings.

Arrebola|Juan P|JP|
Belhassen|Hidaya|H|
Artacho-Cordón|Francisco|F|
Ghali|Ridha|R|
Ghorbel|Hayet|H|
Boussen|Hamouda|H|
Perez-Carrascosa|Francisco M|FM|
Expósito|José|J|
Hedhili|Abderrazek|A|
Olea|Nicolás|N|

Breast cancer
Organochlorine pesticides
Polychlorinated biphenyls
Endocrine disruptors
Persistent organic pollutants


Bio-analytical liquid chromatographic-based method with a mixed mode online solid phase extraction for drug monitoring of fluconazole in human serum.

Abstract: A simple, cost-effective and sensitive liquid chromatography-based bio-analytical method has been developed and validated for therapeutic drug monitoring of fluconazole (FLUC) in human serum. Integration of online mixed-mode solid-phase extraction (SPE) into the analytical system was the key for direct injection of untreated serum samples. A short protein-coated (PC) µBondapak CN silica column (PC-µB-CN-column) as a SPE tool and phosphate buffer saline (PBS) (pH 7.4) as an eluent were applied in the extraction step. PC-µB-CN-column operates in two different chromatographic modes. Using PBS, proteins were extracted from serum samples by size-exclusion liquid chromatography, while FLUC trapping was reversed-phase liquid chromatography dependent. FLUC was then eluted from the PC-µB-CN-column onto the quantification position using a mixture of acetonitrile-distilled deionized water (20:80, v/v) as an eluent and ODS analytical column. FLUC was separated at ambient temperature (22 ± 1 °C) and detected at 260 nm. The method was linear over the range of 200-10000 ng/mL. FLUC recovery in untreated serum samples ranged from 97.8 to 98.8% and showed good accuracy and precision. The reliability of the developed method was evaluated by studying the pharmacokinetic profile of FLUC in humans after an oral administration of a single 150 mg tablet.

Zarad|Walaa|W| El-Gendy|Heba|H| Bazan|Lamyaa|L| Ali|Ahmed|A| Aboulella|Yasmine|Y| Kamal|Maha|M| Emara|Samy|S| Shawky|Ahmed|A|

protein-coated µBondapak CN silica column


Gallbaldder perforation causing a subcutaneous abscess.

Abstract:
INTRODUCTION
This is a report of a rare case of an old woman with a large round mass in the right hypochondrium that was proven to be an abscess.

PRESENTATION OF CASE
A 82-year old woman with a firm round mass in the right hypochondrium was admitted for evaluation. The abdominal CT showed an abscess produced by a gallbladder perforation, and a gallstone impacted at the Hartmann's pouch.

DISCUSSION
The abscess was treated with a transcutaneous paracentesis, while the stone passed to the gastrointestinal tract through a cholecystoenteric fistula, without causing any further problems.

CONCLUSION
Gallbaldder perforation can rarely create a subcutaneous abscess especially in thin, elder subjects. Abscess drainage is the first line of treatment.

Misiakos|Evangelos|E| Tzepi|Ira|I| Brountzos|Ilias|I| Zavras|Nick|N| Charalampopoulos|Anestis|A| Macheras|Anastasios|A|

Perforation
Abscess
Cholecystoenteric fistula
Drainage
Gallbadder