Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease.

Abstract: Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.

Schultz|Stephanie A|SA|
Strain|Jeremy F|JF|
Adedokun|Adedamola|A|
Wang|Qing|Q|
Preische|Oliver|O|
Kuhle|Jens|J|
Flores|Shaney|S|
Keefe|Sarah|S|
Dincer|Aylin|A|
Ances|Beau M|BM|
Berman|Sarah B|SB|
Brickman|Adam M|AM|
Cash|David M|DM|
Chhatwal|Jasmeer|J|
Cruchaga|Carlos|C|
Ewers|Michael|M|
Fox|Nick N|NN|
Ghetti|Bernardino|B|
Goate|Alison|A|
Graff-Radford|Neill R|NR|
Hassenstab|Jason J|JJ|
Hornbeck|Russ|R|
Jack|Clifford|C|
Johnson|Keith|K|
Joseph-Mathurin|Nelly|N|
Karch|Celeste M|CM|
Koeppe|Robert A|RA|
Lee|Athene K W|AKW|
Levin|Johannes|J|
Masters|Colin|C|
McDade|Eric|E|
Perrin|Richard J|RJ|
Rowe|Christopher C|CC|
Salloway|Stephen|S|
Saykin|Andrew J|AJ|
Sperling|Reisa|R|
Su|Yi|Y|
Villemagne|Victor L|VL|
Vöglein|Jonathan|J|
Weiner|Michael|M|
Xiong|Chengjie|C|
Fagan|Anne M|AM|
Morris|John C|JC|
Bateman|Randall J|RJ|
Benzinger|Tammie L S|TLS|
Jucker|Mathias|M|
Gordon|Brian A|BA|
|||

Neurofilament
White matter
Alzheimer's disease
Blood-based biomarkers
Neurodegeneration
Neuroimaging


Chromatographic behavior of new deazapurine ribonucleosides in hydrophilic interaction liquid chromatography.

Abstract: The chromatographic behavior of new biogenic purine nucleosides in hydrophilic interaction liquid chromatography was examined on three different stationary phases, namely bare silica, and amide- and cyclofructan-based stationary phases. The effects of buffer concentration, pH and acetonitrile-to-aqueous-part ratio in the mobile phase on retention and peak shape were assessed. The retention coefficients and peak symmetry values substantially differed with respect to analytes´ structures, stationary phase properties and mobile phase composition. The bare silica column was unsuitable for these compounds under the chromatographic conditions tested due to very broad and asymmetrical peaks. Furthermore, the cyclofructan-based stationary phase provided almost Gaussian peak shapes of all deazapurine nucleosides under most conditions tested. Therefore, the cyclofructan-based stationary phase is the most suitable choice for the chromatographic analysis of nucleosides.

D057927:Hydrophobic and Hydrophilic Interactions

Hydrophilic interaction liquid chromatography


Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.

Abstract: Do immature lungs have air-blood barriers that are more permeable to inhaled nanoparticles than those of fully developed mature lungs? Data supporting this notion and explaining the underlying mechanisms do not exist as far as we know. Using a rat model of postnatal lung development, here the data exactly supporting this notion, that is, significantly more gold nanoparticles (NPs) cross from the air space of the lungs to the rest of the body in neonates than in adults, are presented. Moreover, in neonates the translocation of gold NPs is not size dependent, whereas in adult animals smaller NPs cross the air-blood lung barrier much more efficiently than larger NPs. This difference in air-blood permeability in neonate versus adult animals suggests that NP translocation in the immature lungs may follow different rules than in mature lungs. Supporting this notion, we propose that the paracellular transport route may play a more significant role in NP translocation in immature animals, as suggested by protein expression studies. Findings from this study are critical to design optimal ways of inhalation drug delivery using NP nanocarriers for this age group, as well as for better understanding of the potential adverse health effects of nanoparticle exposures in infants and young children.

Tsuda|Akira|A|0000-0003-4542-1573
Donaghey|Thomas C|TC|
Konduru|Nagarjun V|NV|
Pyrgiotakis|Georgios|G|
Van Winkle|Laura S|LS|
Zhang|Zhenyuan|Z|
Edwards|Patricia|P|
Bustamante|Jessica-Miranda|JM|
Brain|Joseph D|JD|
Demokritou|Phillip|P|

translocation
nanoparticles
paracellular transport route
infant
E-cadherin
air−blood lung barrier
postnatal developing lung


HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer.

Abstract:
BACKGROUND
Gastric cancer (GC) is one of the most prevalent and deadly malignancies worldwide. Accumulating reports have indicated the participation of long non-coding RNAs (lncRNAs) in the onset and progression of GC.

METHODS
GSE109476 data was utilized to screen out lncRNAs dysregulated in GC. Gene expressions were determined by qRT-PCR and western blot. Both in vitro and in vivo experiments were carried out to assess the function of HOXC-AS1 in GC. The association between genes was verified via RIP, ChIP, CoIP, RNA pull down and luciferase reporter assays, as appropriate.

RESULTS
HOXC-AS1 was discovered to be upregulated in GC and located both in cytoplasm and in nucleus in GC cells. Functionally, inhibition of HOXC-AS1 restrained GC cell growth and metastasis both in vitro and in vivo. Moreover, HOXC-AS1 was proved to be trans-activated by c-MYC in GC. In return, HOXC-AS1 positively regulated MYC expression in GC through targeting miR-590-3p/MYC axis in cytoplasm and modulating BRG1/β-catenin complex-activated MYC transcription in nucleus. Furthermore, the rescue assays verified that MYC mediated HOXC-AS1-affected GC progression.

CONCLUSION
Our research illustrated a feedback loop of HOXC-AS1-MYC in aggravating GC cell growth and metastasis, highlighting HOXC-AS1 as a promising target for GC diagnosis and treatment.

Dong|Yangyang|Y| Li|Xinyu|X| Lin|Zhibin|Z| Zou|Wenbing|W| Liu|Yan|Y| Qian|Huiyang|H| Jia|Jing|J|

D015972:Gene Expression Regulation, Neoplastic


Immediate pneumothorax after neurosurgical procedures.

Abstract:
OBJECTIVE
Pneumothorax after neurosurgical procedures is very rare and incompletely understood. This study was performed to explore the clinical characteristics and pathogenesis of pneumothorax after neurosurgery.

METHODS
We retrospectively evaluated patients admitted from December 2016 to April 2019 for treatment of spontaneous intracranial hemorrhage. The inclusion criteria were neurosurgical procedures (open surgeries or endovascular intervention) performed under general anesthesia, no performance of central venous puncture during surgery, and occurrence of pneumothorax immediately after the neurosurgical procedure.

RESULTS
Eight patients developed pneumothorax after neurosurgical procedures for spontaneous intracranial hemorrhage under general anesthesia. Of the eight patients, seven had aneurysmal subarachnoid hemorrhage and one had left temporal-parietal hemorrhage. The lung injury prediction score (LIPS) was 3, 4, 5, 6, and 9.5 in three, one, two, one, and one patient, respectively. During the operation, volume-controlled ventilation (tidal volume, 8-10 mL/kg) was selected for all patients.

CONCLUSIONS
Neurogenic pulmonary edema, inappropriate mechanical ventilation, and stimulation by endotracheal intubation might conjointly contribute to postoperative pneumothorax. To avoid this rare entity, mechanical ventilation with a low tidal volume or low pressure during general anesthesia should be adopted for patients with hemorrhagic cerebrovascular diseases involving the temporal lobe and a LIPS of >3.

pneumothorax
Neurosurgical procedure
lung injury
lung injury prediction score
neurogenic pulmonary edema
mechanical ventilation
thoracic closed drainage


Optimization of Prepectoral Breast Reconstruction.

Abstract:
Introduction
Acellular dermal matrix (ADM) were introduced in the early 2000s and more recently permitted new protocols for breast reconstruction allowing a short operative time with improved outcomes until the new muscle-sparing breast reconstruction proposed in 2014 using the Braxon® ADM. The aim of this research is to propose a technique to improve the aesthetic outcome using Braxon ADM with prepectoral implants.

Materials and Methods
The enrolled patients were submitted to a nipple skin-sparing mastectomy leaving 1 additional centimeter of subcutis on the proximal part of the upper pole of the breast (see Surgical Technique). Aesthetic outcomes were compared to those obtained with traditional breast reconstruction with prosthesis and the Braxon ADM placed in the prepectoral space. Mean values of aesthetic outcomes were analyzed using the Student t test, and the κ test was used to analyze interobserver variability.

Results
The overall aesthetic score was improved of 29.6% of the patients; in particular the most improved score was that for contour (+98.01%). Statistical significance was found for contour, upper pole definition, and total score average (p < 0.05). The κ test showed interobserver variability with a good level of agreement on contour (κ = 0.832).

Conclusions
The proposed technique has allowed attainment of good results in terms of aesthetic outcomes. In a small sample we did not register any particular complications but we verified a better satisfaction on the evaluation of the aesthetic result (level of evidence: 3).

Cuomo|Roberto|R|
Giardino|Francesco Ruben|FR|
Neri|Alessandro|A|
Nisi|Giuseppe|G|
Brandi|Cesare|C|
Zerini|Irene|I|
Jingjian|Han|H|
Grimaldi|Luca|L|

Breast
Breast reconstruction
Acellular dermal matrix
Braxon
Breast cancer


Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer.

Abstract:
Background
Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy.

Materials and Methods
We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions.

Results
Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation.

Conclusions
The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.

Galli|Giulia|G|
Bregni|Giacomo|G|
Cavalieri|Stefano|S|
Porcu|Luca|L|
Baili|Paolo|P|
Hade|Amash|A|
Di Salvo|Francesca|F|
Sant|Milena|M|
Agresti|Roberto|R|
Gennaro|Massimiliano|M|
Folli|Secondo|S|
De Santis|Maria C|MC|
Paolini|Biagio|B|
Carcangiu|Maria L|ML|
de Braud|Filippo|F|
Di Cosimo|Serena|S|

Breast cancer
Residual disease
Endocrine therapy
Chemotherapy, neoadjuvant


Flavonoids of Tripodanthus acutifolius inhibit TNF-α production in LPS-activated THP-1 and B16-F10 cells.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
T. acutifolius is an endemic species from South America which has been used in traditional medicine since ancient times due to its biological properties, including its anti-inflammatory effects.

AIM OF THE STUDY
The aim of the article is to investigate the inhibitory activity of T. acutifolius over TNF-α production in THP-1 and B16-F10 cells. To achieve this, phytochemical analysis has been used to determine the compounds present in the species with anti-inflammatory effects.

MATERIALS AND METHODS
Leaves and stems of T. acutifolius were extracted with n-heptane, dichloromethane, methanol and water. The resulting extracts were analysed in THP-1 and B16-F10 cells by measuring their inhibitory capacity over the production of TNF-α stimulated with LPS.

RESULTS
The guided-bioassay led to the isolation of 6,2',4'-trimethoxyflavone (1), 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone (2), (E)-2',4'-dihydroxy-6'-methoxy-chalcone (3) and 5,4'-dihydroxy-6,7,8-trimethoxyflavone (4) from the dichloromethanic extract. Compounds showed an inhibitory activity of TNF-⍺ production in THP-1 cells, with IC50 of 2.38 ± 0.02 μM, 12.36 ± 0.17 μM, 1.12 ± 0.01 μM and 8.09 ± 0.04 μM, respectively. In addition, the compounds showed an inhibitory activity of TNF-⍺ production in B16-F10 cells with IC50 of 1.32 ± 0.03 μM, 5.63 ± 0.09 μM, 0.60 ± 0.02 μM and 3.77 ± 0.15 μM, respectively.

CONCLUSIONS
We identified 3 flavones (6,2',4'-trimethoxyflavone, 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone, 5,4'-dihydroxy-6,7,8-trimethoxyflavone) and a chalcone ((E)-2',4'-dihydroxy-6'-methoxy-chalcone) present in the leaves and stems of T. acutifolius. These compounds are an alternative for the treatment of immune-mediated inflammatory disorders, acting as negative modulators over the TNF-α production.

Apaza T|L|L|
Serban|Andreea Madalina|AM|
Cabanillas|A H|AH|
Villacampa|A|A|
Rumbero|Angel|A|

Flavonoids Tripodanthus Chalcones Anti–inflammatory TNF–α


Rethinking temperature effects on leaf growth, gene expression and metabolism: Diel variation matters.

Abstract: Plants have evolved to grow under prominently fluctuating environmental conditions. In experiments under controlled conditions, temperature is often set to artificial, binary regimes with constant values at day and at night. This study investigated how such a diel (24 hr) temperature regime affects leaf growth, carbohydrate metabolism and gene expression, compared to a temperature regime with a field-like gradual increase and decline throughout 24 hr. Soybean (Glycine max) was grown under two contrasting diel temperature treatments. Leaf growth was measured in high temporal resolution. Periodical measurements were performed of carbohydrate concentrations, carbon isotopes as well as the transcriptome by RNA sequencing. Leaf growth activity peaked at different times under the two treatments, which cannot be explained intuitively. Under field-like temperature conditions, leaf growth followed temperature and peaked in the afternoon, whereas in the binary temperature regime, growth increased at night and decreased during daytime. Differential gene expression data suggest that a synchronization of cell division activity seems to be evoked in the binary temperature regime. Overall, the results show that the coordination of a wide range of metabolic processes is markedly affected by the diel variation of temperature, which emphasizes the importance of realistic environmental settings in controlled condition experiments.

Kronenberg|Lukas|L|0000-0002-2840-7676
Yates|Steven|S|
Ghiasi|Shiva|S|
Roth|Lukas|L|0000-0003-1435-9535
Friedli|Michael|M|
Ruckle|Michael E|ME|
Werner|Roland A|RA|0000-0002-4117-1346
Tschurr|Flavian|F|
Binggeli|Melanie|M|
Buchmann|Nina|N|0000-0003-0826-2980
Studer|Bruno|B|0000-0001-8795-0719
Walter|Achim|A|

controlled conditions
circadian
fluctuating temperature
natural environment
storage carbohydrates


The United States opioid epidemic: a review of the surgeon's contribution to it and health policy initiatives.

Abstract: Opioid abuse and addiction is causing widespread devastation in communities across the USA and resulting in significant strain on our healthcare system. There is increasing evidence that prescribers are at least partly responsible for the opioid crisis because of overprescribing, a practice that developed from changes in policy and reimbursement structures. Surgeons, specifically, have been subject to scrutiny as 'adequate treatment' of post-surgical pain is poorly defined and data suggest that many patients receive much larger opioid prescriptions than needed. The consequences of overprescribing include addiction and misuse, dispersion of opioids into the community, and possible potentiation of illicit drug/heroin use. Several solutions to this crisis are currently being enacted with variable success, including Prescription Drug Monitoring Programmes, policy-level interventions aimed to de-incentivize overprescribing, limiting opioid exposures through Enhanced Recovery After Surgery protocols, and the novel idea of creating surgery- and/or procedure-specific prescribing guidelines. This problem is likely to require not one, but several potential solutions to reverse its trajectory. It is critical, however, that we as physicians and prescribers find a way to stop the needless overprescribing while still treating postoperative pain appropriately.

Theisen|Katherine|K| Jacobs|Bruce|B| Macleod|Liam|L| Davies|Benjamin|B|

D000701:Analgesics, Opioid
D058872:Epidemics
D006291:Health Policy
D006801:Humans
D057970:Inappropriate Prescribing
D009293:Opioid-Related Disorders
D015279:Organizational Culture
D010149:Pain, Postoperative
D010818:Practice Patterns, Physicians'
D066231:Surgeons
D014481:United States

opioid surgeons overprescribing pain postoperative #UroBPH analgesics


Alternative neural circuitry that might be impaired in the development of Alzheimer disease.

Abstract: It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as Aβ or tau protein present in different areas of the brain could be important.

Avila|Jesus|J|
Perry|George|G|
Strange|Bryan A|BA|
Hernandez|Felix|F|

cognitive decline
tau proteins
Alzheimer disease (AD)
abeta
tauopathies


Anisotropic Characterizations of Electrospun PAN Nanofiber Mats Using Design of Experiments.

Abstract: This paper deals with the dielectric and mechanical characterizations of polyacrylonitrile (PAN)-aligned electrospun nanofiber mats. A two factor three level full factorial experiment is conducted to understand the effect of various parameters on dielectric and mechanical responses. These responses are recorded against randomly oriented and aligned nanofiber mats. Improved properties of electrospun mats have applications in the field of energy storage and nanocomposite reinforcement. Dielectric and mechanical characterizations of PAN mats are vital, as the aligned electrospun mats were found to be useful in advanced energy and mechanical reinforcement applications. Therefore, it is paramount to understand the effects of system parameters to these properties. The design of experiment (DoE) includes two factors and three level full factorial experiments with concentrations of PAN solutions at 8 wt.%, 9 wt.%, and 10 wt.%, and speed of the rotating mandrel (collector) at 3 volt (V), 4 V, and 5 V inputs. The electric field intensity used in the experiment is 1 kV/cm. DoE is conducted to understand the nonlinear interactions of parameters to these responses. The dielectric and mechanical characterizations of 8 wt.%, 9 wt.%, and 10 wt.% with different speeds for the original and improved systems are discussed. It was observed that at 9 wt.% and at all mandrel speeds, the dielectric and tensile properties are optimum.

design of experiment
dielectric
tensile
electrospun fibers


What does a mathematical model tell about the impact of reinfection in korean tuberculosis infection?

Abstract:
OBJECTIVES
According to the Korea Centers for Disease Control and Prevention, new active tuberculosis (TB) cases have increased since 2001. Some key factors explain and characterize the transmission dynamics of Korean TB infection, such as a higher ratio of latent individuals and a new reporting system implemented in 2001, among others.

METHODS
We propose a mathematical TB model that includes exogenous reinfection to gain a better understanding of the recent trend for TB incidence. We divide the simulation time window into two periods, 1970-2000 and 2001-2012, according to the implementation date of a new TB detection system.

RESULTS
Two sets of parameters, including the transmission rate, the latent period, the recovery rate, and the proportion of exogenous reinfection, are estimated using the least-squares method and calibrated to data on the incidence of active TB.

CONCLUSION
Among some key parameters in the model, the case finding effort turned out to be the most significant impacting component on the reduction in the active TB cases.

Kim|Sara|S| Choe|Seoyun|S| Kim|Junseong|J| Nam|Sanga|S| Shin|Yeon|Y| Lee|Sunmi|S|

Tuberculosis
Korea
Exogeneous reinfection
Tuberculosis control measures


How much does household food insecurity explain income inequalities in untreated dental caries?

Abstract:
BACKGROUND
The pathway by which socioeconomic disadvantages are manifested in the occurrence of dental caries remains unclear.

AIM
To explore how much the association between untreated dental caries and income inequalities is related to household food insecurity (HFI).

DESIGN
A population-based study was conducted with a sample of 466 12-year-old students. Dental caries was evaluated by an examiner who had undergone calibration exercises. HFI was assessed using the Food Insecurity Scale validated for Brazilian Portuguese. Poisson regression models were created to determine associations between dental caries and both household income and HFI. The proportion of the income effect on dental caries explained by HFI was determined by the variation in percentages between the crude prevalence ratio (PRc ) for dental caries and this measure adjusted by HFI (PRa ).

RESULTS
The prevalence of dental caries was higher among children from families with a per capita household income lower than US$ 71 (PR: 1.69; 95%CI: 1.15-2.49) or from US$ 71 to US$ 142 (PR: 1.50; 95%CI: 1.04-2.17). Moreover, 14% of the association between a low income and dental caries was explained by HFI.

CONCLUSIONS
Differences in the prevalence of dental caries in schoolchildren related to socioeconomic inequalities could partially be attributed to HFI in low-income families.

food insecurity
income
dental caries
child
cross-sectional study


Correlations between clinical signs and corneal cytology in feline eosinophilic keratoconjunctivitis.

Abstract:
OBJECTIVE
To assess correlations between clinical and cytological features of feline eosinophilic keratoconjunctivitis at the time of cytological diagnosis.

ANIMALS STUDIED
Fifteen client-owned, domestic breed cats (18 eyes) examined between 2007 and 2019.

PROCEDURES
An electronic search and medical record review of cats diagnosed with feline eosinophilic keratitis or keratoconjunctivitis (FEK) based on clinical examination findings and eosinophils detected on corneal cytology were conducted. Clinical severity was graded using a modified version of a previously validated semiquantitative preclinical ocular toxicology scoring (SPOTS) system. Clinical grades were assigned following review of clinical images and medical record descriptions, and cytological grades were assigned following review of archived corneal cytology slides. Correlations were analyzed for significance using Spearman's rank correlation coefficient.

RESULTS
Higher total corneal scores correlated with higher total conjunctival scores, but not with total fluorescein scores. Small lymphocyte scores correlated negatively with scores for collagen degeneration or mineralization. Globule leukocytes, a unique cell type not previously described in ocular cytology, were identified in 4 of 18 cytological samples. Higher globule leukocyte scores were correlated with higher scores for mast cells or plasma cells. Specimens with lower eosinophil scores had higher globule leukocyte scores.

CONCLUSIONS
Large variability was detected in the cytological characteristics and clinical features of FEK-affected cats. This is the first report of globule leukocytes being identified in ocular cytology from any species. The role of globule leukocytes in the etiopathogenesis and progression of FEK remains unknown and warrants further investigation.


Preparation and characterization of novel eggshell membrane-chitosan blend films for potential wound-care dressing: From waste to medicinal products.

Abstract: A series of different eggshell membrane (ESM) and chitosan (CS) blend films (ESM/CS) were prepared for wound-care dressing. The appearance, transparency and microstructure of the films were characterized. Several wound care-related properties such as the film integrity in solution, pH, protein (BSA) and wound fluid absorption capacity as well as the antibacterial property of ESM/CS films were evaluated. The blend films were more stable than CS film after 95 h of incubation in solution. The integrity of the blend films improved significantly at the cost of a small insignificant decrease in wound fluid absorption capacity. Besides, the blend films provided an acidic environment (pH = 5.86) for wound healing. The swelling properties of ESM contributed significantly to the increase of BSA absorption capacity of the blend films (from 46.57 mg/g of CS film to 61.07 mg/g of blend film) and helped absorb more nutrients to promote the proliferation and migration of fibroblasts. Addition of CS to ESM also enhanced the antibacterial activity of the films significantly. The results indicated that the EMS/CS blend films with 0.01 g ESM/mL CS solution showed the highest high potential to be used as a wound-care dressing for humans as well as animals.

Li|Xiaoyun|X|
Ma|Meihu|M|
Ahn|Dong Uk|DU|
Huang|Xi|X|

Eggshell membrane
Wound healing
Antibacterial activity


Comparison of absorption kinetics and utilisation of DL-methionine (DL-Met), Met-Met product (AQUAVI® Met-Met), and protein-bound methionine (PB-Met) by female broiler chickens.

Abstract: 1. Two experiments were conducted to determine the effects of different methionine (Met) sources regarding their absorption kinetics and utilisation in female single-meal-fed broiler chickens.2. A total of 340, one day old female Ross 308 broiler chickens were fed commercial starter and grower diets for 38 d. Birds were then allocated to treatment diets in two experiments as a completely randomised design with four replicates of five chicks per each until 60 d of age. In experiment 1, a 2 × 5 factorial design was used to investigate the effect of two sources (DL-Met and AQUAVI®Met-Met) and five equimolar levels (0.4, 0.8, 1.2, 1.6, and 2 g/kg) in the diet. In experiment 2, different proportions of protein-bound methionine (PB-Met) to DL-Met (0.4:1.6, 0.8:1.2, 1.2:0.8: 1.6:0.4, and 2:0 g/kg) were incorporated into a basal diet deficient in Met. During the experiment, chickens received 90 g of pelleted feed for a time period of 17 ± 2.5 min, once daily.3. The results indicated that chickens fed diets supplemented with DL-Met and Met-Met showed a rapid rise in plasma Met 1 h after feeding, with a sudden drop at 2 h after feeding. In contrast, chickens fed PB-Met substituted diets showed a gradual plasma peak at 1 and 2 h postprandial (P < 0.01). Plasma homocysteine (HCY) content increased to 34.38 and 40.43 μmol/l with DL-Met2.0 and Met-Met2.0 diets, while it decreased to 25.68 μmol/l with PB-Met2.0(P ≤ 0.01). Chickens that received the PB-Met2.0 diet had higher (P ≤ 0.01) protein utilisation (0.54 g/g) and lower excreta nitrogen content (4.04 g/100 g excreta), which demonstrated the benefits of feeding a protein-bound Met source. The efficiency of Met utilisation was 0.69 g/g in chickens fed PB-Met2.0 diet, but only 0.36 and 0.41 g/g in those fed DL-Met2.0 and Met-Met2.0 (P ≤ 0.01).4. The observed utilisation coefficient of DL-Met and Met-Met for single-meal meat-type chickens was lower than expected. The synchronisation of intestinal Met absorption maintained the efficiency of utilisation, which was related to the sources of added Met, with protein-bound Met showing the best utilisation and least excretion.

D000824:Animal Nutritional Physiological Phenomena

homocysteine
excreta nitrogen content
Protein efficiency
amino acid imbalance
glutathione


Quality of life and safety impact of COVID-19 associated smell and taste disturbances.

Abstract:
OBJECTIVE
The association between COVID-19 and chemosensory loss has garnered substantial attention, however to date little is known about the real-life consequences of impairment in this unique patient population. The aim of this study is to evaluate the quality of life (QOL) and personal safety deficits experienced by patients with COVID-19 infection.

STUDY DESIGN
Prospective, longitudinal questionnaires.

SETTING
National survey.

METHODS
A longitudinal web-based nationwide survey of adults with COVID-19 and/or a sudden change in smell and taste was launched April 10, 2020. Previously published questions on chemosensory-related QOL and safety events were asked at the 6-month follow-up survey.

RESULTS
As of February 10, 2021, 480 eligible respondents took the 6-month questionnaire, of whom 322 were COVID-19 positive. Impact on QOL was substantial with 96% of subjects reporting at least one of the defined deficits, and over 75% reporting at least 3 of these. "Reduced enjoyment of food" was the most common complaint (87%), while 43% of subjects self-reported depression. The prevalence of safety-related issues was common in this population, with over 57% reporting at least one, and 36% reporting 2 or more events. Of the events asked, the inability to smell smoke that others could perceive was the most common at 45%.

CONCLUSIONS
COVID-19 associated chemosensory losses have a real and substantial impact on both quality of life and safety, beyond mere inconvenience. The high prevalence of these issues despite a relatively short period of olfactory deficit should alert clinicians to the serious risks to an already vulnerable patient population.

Coelho|Daniel H|DH|
Reiter|Evan R|ER|
Budd|Serenity G|SG|
Shin|Yongyun|Y|
Kons|Zachary A|ZA|
Costanzo|Richard M|RM|

COVID-19
Smell
Taste
Coronavirus
Epidemiology
Quality of life, safety


A Review: Phytochemicals Targeting JAK/STAT Signaling and IDO Expression in Cancer.

Abstract: Cancer remains a major health problem worldwide. Among many other factors, two regulatory defects that are present in most cancer cells are constitutive activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and the induction of indoleamine 2, 3-dioxygenase (IDO), an enzyme that catalyzes tryptophan degradation, through JAK/STAT signaling. Cytokine signaling activates STAT proteins in regulating cell proliferation, differentiation, and survival through modulation of target genes. Many phytochemicals can inhibit both JAK/STAT signaling and IDO expression in antigen-presenting cells by targeting different pathways. Some of the promising phytochemicals that are discussed in this review include resveratrol, cucurbitacin, curcumin, (-)-epigallocatechin gallate, and others. It is now evident that phytochemicals play key roles in inhibition of tumor proliferation and development and provide novel means for therapeutic targeting of cancer.

Arumuggam|Niroshaathevi|N|
Bhowmick|Neil A|NA|
Rupasinghe|H P Vasantha|HP|

phytochemicals
JAK/STAT
cancer
indoleamine 2, 3-dioxygenase (IDO)
epigenetics


Mandibular tumour as the primary manifestation of an occult adenocarcinoma.

Abstract: Oral cavity is an uncommon site for occurrence of metastasis and usually indicates widespread systemic disease. Primary tumours from the lung most commonly metastasise to oral soft tissues (31.3%) and jaw bones (22%) among men. It is quite challenging to diagnose a solitary metastatic lesion and to determine the site of primary lesion, due to the rarity of these occurrences. This case report describes the jaw bone as a first sign of occult primary lung adenocarcinoma with multiple metastases in 47-year-old man. The patient was treated with the combination of carboplatin and paclitaxel, and has completed two cycles till date with a stable clinical course. Diagnosis of metastatic carcinoma of jaw is very challenging. The pathologist must have knowledge of ancillary techniques along with clinical, radiological and histological correlation to determine the origin of distant primary.

Kaur|Harpreet|H| Mishra|Deepika|D| Manchanda|Smita|S| Bhutia|Ongkila|O|

D000971:Antineoplastic Combined Chemotherapy Protocols

cancer - see oncology
dentistry and oral medicine
lung cancer (oncology)
pathology


Phase behavior of ABC-type triple-hydrophilic block copolymers in aqueous solutions.

Abstract: The phase behavior of symmetric ABC triple-hydrophilic triblock copolymers in concentrated aqueous solutions is investigated using a simulated annealing technique. Two typical cases, in which the hydrophilicity of the middle B-block is either stronger or weaker than that of the end A- and C-blocks, are studied. In these two cases, a variety of phase diagrams are constructed as a function of the volume fraction of the B-block and the copolymer concentration ([Formula: see text] for both non-frustrated and frustrated copolymers. Structures, such as two-color alternatingly packed cylinders or gyroid, and lamellae-in-lamellae etc. that do not occur in the melt system, are obtained in solutions. Rich phase transition sequences, especially re-entrant phase transitions involving complex continuous networks of alternating gyroid and alternating diamond are observed for a given copolymer with decreasing [Formula: see text] . The difference in hydrophilicity among different blocks can result in inhomogeneous distribution of solvent molecules in the morphology, and with the decrease of [Formula: see text] , the distribution of solvent molecules presents a non-monotonic variation. This results in a non-monotonic variation of the effective volume fraction of each domain with the decrease of [Formula: see text] , which induces the re-entrant phase transitions. The presence of a good solvent for all the blocks can cause changes in the effective segregation strengths between different blocks and also in chain conformations, hence can alter the bulk phases and results in the occurrence of new structures and phase transitions. Especially, structures having A-C interfaces or A-C mixed domains can be obtained even in the non-frustrated copolymer systems, and structures obtained in the frustrated systems may be similar to those obtained in the non-frustrated systems. The window of the alternating gyroid structures may occupy a large part of the phase diagram for non-frustrated copolymers with stronger B-hydrophilicity. This behavior can be used to tune the self-assembled structures of block copolymers.

Zheng|Lingfei|L| Wu|Jianqi|J| Wang|Zheng|Z| Yin|Yuhua|Y| Jiang|Run|R| Li|Baohui|B|

Soft Matter: Polymers and Polyelectrolytes


Adjacent Bilateral Stress Pedicle Fractures after Instrumented Lumbar Fusion: A Case Report.

Abstract: Bilateral pedicle stress fractures are rare even in the elderly. Bilateral pedicle fractures are due to post-surgical complications at the level of fusion or stress related activities in most cases. The authors describe a unique case of adjacent L4 bilateral pedicle fractures, which developed 4 years after anterior lumbar interbody fusion with bone cement augmented screw fixation at the L5-S1 level. As far as the authors' knowledge, no similar case has been previously reported in the literature. The pathophysiological mechanism of this rare entity is discussed with review of relevant literature.

Kim|Hak Sung|HS|
Ha|Sang Woo|SW|
Ju|Chang Il|CI|
Kim|Seok Won|SW|

Fractures bone
Lumbar vertebrae
Spinal fusion


The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development.

Abstract: Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression), are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase-variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.

Tan|Aimee|A|
Atack|John M|JM|
Jennings|Michael P|MP|
Seib|Kate L|KL|

vaccine
phase variation
DNA methyltransferase
epigenetics
DNA modification enzyme
gene expression


Gastrointestinal stromal tumors during pregnancy: a systematic review of an uncommon but treatable malignancy.

Abstract: Although modern social structure and medical advances have led to the increasing number of women childbearing in older age, cancer remains a rare diagnosis during pregnancy. There is little given information throughout the literature concerning gestation associated with the coexistence of gastrointestinal stromal tumor (GIST). In this review, we present 12 reported cases of GIST during pregnancy and we discuss the maternal and fetal outcome, as well as the therapeutic plan that was followed in each situation. From the collected data, 8 out of 12 cases had an uneventful outcome of their fetus. In 11 out of 12 cases surgical excision of the tumor was the treatment of choice, while seven women were treated with imatinib. Two of them were already on imatinib therapy during conception due to preexisting GIST diagnosis. Surgery remains the gold standard for the treatment of local or resectable GIST, while published data concerning the use of imatinib during pregnancy indicate that teratogenicity or fetal loss might be induced, especially if given during the first trimester of pregnancy. GIST during gestational period is a rare tumor in which a multidisciplinary approach should be designed, taking always into consideration that it has a favorable outcome on targeted treatment.

D013505:Digestive System Surgical Procedures

Gastrointestinal stromal tumor
Pregnancy
Gestation
GIST
Imatinib


Microvasculature of carotid atheromatous plaques: hemorrhagic plaques have dense microvessels with fenestrations to the arterial lumen.

Abstract:
BACKGROUND
Microvessels in atheromatous plaques are well known to play a role in plaque vulnerability associated with intraplaque hemorrhage, but their architecture remains unclear. The morphometry of the microvasculature and hemorrhage of human carotid atheromatous plaques (CAPs) were evaluated, and 3-dimensional (3D) reconstruction of the microvessels was performed.

METHODS
CAPs were obtained by endarterectomy in 42 patients. The specimens were analyzed using light microscopy. Plaque hemorrhage was defined as an area-containing red blood cells (>1 mm2). To determine the histopathologic features of plaque hemorrhage, the plaque area was divided into 4 regions: cap, shoulder, lipid/necrotic core, and media. Then, the density of microvessels and macrophages in each region was quantified. Two representative lesions with either hemorrhagic or nonhemorrhagic plaque were cut into 90 serial sections. The sections were double stained with anti-CD34 and anti-α smooth muscle actin antibodies, scanned using a digital microscope, and reconstructed using TRI-SRF2 software.

RESULTS
The hemorrhagic plaques showed a higher density of microvessels than nonhemorrhagic plaques in the shoulder, cap, and lipid/necrotic core (P=.03, .009, and .001, respectively), and there was positive correlations between its density and macrophages in each regions (P<.001, .001, and .019, respectively). 3D imaging also revealed dense microvessels with a network structure in the cap and shoulder regions of hemorrhagic plaques, and some of the vessels were fenestrated to the arterial lumen.

CONCLUSIONS
The microvasculature of plaques with intraplaque hemorrhage was dense, some of which fenestrated to the arterial lumen. The pathologic 3D imaging revealed precise architecture of microvasculature of plaques.

Kurata|Mie|M| Nose|Masato|M| Shimazu|Yoshihito|Y| Aoba|Takaaki|T| Kohada|Yuki|Y| Yorioka|Soichiro|S| Suehiro|Satomi|S| Fukuoka|Erina|E| Matsumoto|Shirabe|S| Watanabe|Hideaki|H| Kumon|Yoshiaki|Y| Okura|Takafumi|T| Higaki|Jitsuo|J| Masumoto|Junya|J|

D002339:Carotid Arteries
D016893:Carotid Stenosis
D016894:Endarterectomy, Carotid
D006801:Humans
D055806:Microvessels
D058226:Plaque, Atherosclerotic
D017540:Tunica Media

intraplaque hemorrhage
microvasculature of plaques
Atherosclerosis
three-dimensional imaging


Expandable Immunotherapeutic Nanoplatforms Engineered from Cytomembranes of Hybrid Cells Derived from Cancer and Dendritic Cells.

Abstract: Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. In bilateral tumor-bearing mouse models, the FM-coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post-nanophotosensitizer-induced photodynamic therapy (PDT). The FM-induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy-caused regression of the irradiation-free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor-specific immunotherapy-based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.

D000949:Histocompatibility Antigens Class II

photodynamic therapy
fused cells
homotypic targeting
hybrid cytomembrane
immunotheraputic platform


How did COVID-19 measures impact sexual behaviour and access to HIV/STI services in Panama? Results from a national cross-sectional online survey.

Abstract:
OBJECTIVE
To describe reported changes in sexual behaviours, including virtual sex (sexting and cybersex), and access to HIV/STI testing and care during COVID-19 measures in Panama.

METHODS
We conducted an online cross-sectional survey from 8 August to 12 September 2020 among adults (≥18 years) residing in Panama. Participants were recruited through social media. Questions included demographics, access to HIV/STI testing and HIV care, and sexual behaviours 3 months before COVID-19 social distancing measures and during social distancing measures (COVID-19 measures). Logistic regression was used to identify associations between variables and behavioural changes.

RESULTS
We recruited 960 participants; 526 (54.8%) identified as cis-women, 366 (38.1%) cis-men and 68 (7.1%) non-binary or another gender. The median age was 28 years (IQR: 23-37 years), and 531 of 957 (55.5%) were of mixed ethnicity (mixed Indigenous/European/Afro-descendant ancestry). Before COVID-19 measures, virtual sex was reported by 38.5% (181 of 470) of cis-women, 58.4% (184 of 315) cis-men and 45.0% (27 of 60) non-binary participants. During COVID-19 measures, virtual sex increased among 17.2% of cis-women, 24.7% cis-men and 8.9% non-binary participants. During COVID-19 measures, 230 of 800 (28.8%) participants reported decreased casual sex compared with pre-COVID-19 measures. Compared with pre-COVID-19 measures, decreased casual sex was reported more frequently during COVID-19 measures by cis-men compared with cis-women (39.2% vs 22.9%, urban/rural adjusted OR (AOR)=2.17, 95% CI 1.57 to 3.01), and by Afro-descendant compared with participants of mixed ethnicity (40.0% vs 29.8%, AOR=1.78, 95% CI 1.07 to 2.94). Compared with no change in virtual sex (16.8%), increased virtual sex (38.5%, AOR=1.78, 95% CI 1.10 to 2.88) and decreased virtual sex (86.7%, AOR=16.53, 95% CI 7.74 to 35.27) were associated with decreased casual sex encounters. During COVID-19 measures, HIV/STI testing could not be obtained by 58.0% (58 of 100) of the participants who needed a test, and interrupted HIV care was reported by 53.3% (8 of 15) of participants living with HIV.

CONCLUSIONS
COVID-19 measures in Panama were associated with a decrease in casual sex among cis-men and Afro-descendant people, while access to HIV/STI testing and care was seriously disrupted.


Reduced Empathy Scores in Patients with Parkinson's Disease: A Non-Motor Symptom Associated with Advanced Disease Stages.

Abstract:
BACKGROUND
Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease (PD).

OBJECTIVE
To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients.

METHODS
Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery.

RESULTS
PD patients had a significant lower global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn & Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables.

CONCLUSIONS
PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced.

Schmidt|Nele|N| Paschen|Laura|L| Deuschl|Günther|G| Witt|Karsten|K|

D011569:Psychiatric Status Rating Scales

empathy
Interpersonal Reactivity Index
Parkinson’s disease
Theory of Mind


Global longitudinal strain software upgrade: Implications for intervendor consistency and longitudinal imaging studies.

Abstract:
BACKGROUND
Speckle tracking can be used to measure left ventricular global longitudinal strain (GLS).

AIMS
To study the effect of speckle tracking software product upgrades on GLS values and intervendor consistency.

METHODS
Subjects (patients or healthy volunteers) underwent systematic echocardiography with equipment from Philips and GE, without a change in their position. Off-line post-processing for GLS assessment was performed with the former and most recent upgrades from these two vendors (Philips QLAB 9.0 and 10.2; GE EchoPAC 12.1 and 13.1.1). GLS was obtained in three myocardial layers with EchoPAC 13.1.1. Intersoftware and intervendor consistency was assessed. Interobserver variability was tested in a subset of patients.

RESULTS
Among 73 subjects (65 patients and 8 healthy volunteers), absolute values of GLS were higher with QLAB 10.2 compared with 9.0 (intraclass correlation coefficient [ICC]: 0.88; bias: 2.2%). Agreement between EchoPAC 13.1.1 and 12.1 varied by myocardial layer (13.1.1 only): midwall (ICC: 0.95; bias: -1.1%), endocardium (ICC: 0.93; bias: 1.6%) and epicardial (ICC: 0.80; bias: -3.3%). Although GLS was comparable for QLAB 9.0 versus EchoPAC 12.1 (ICC: 0.95; bias: 0.5%), the agreement was lower between QLAB 10.2 and EchoPAC 13.1.1 endocardial (ICC: 0.91; bias: 1.1%), midwall (ICC: 0.73; bias: 3.9%) and epicardial (ICC: 0.54; bias: 6.0%). Interobserver variability of all software products in a subset of 20 patients was excellent (ICC: 0.97-0.99; bias: -0.8 to 1.0%).

CONCLUSION
Upgrades of speckle tracking software may be associated with significant changes in GLS values, which could affect intersoftware and intervendor consistency. This finding has important clinical implications for the longitudinal follow-up of patients with speckle tracking echocardiography.

Castel|Anne-Laure|AL|
Menet|Aymeric|A|
Ennezat|Pierre-Vladimir|PV|
Delelis|François|F|
Le Goffic|Caroline|C|
Binda|Camille|C|
Guerbaai|Raphaëlle-Ashley|RA|
Levy|Franck|F|
Graux|Pierre|P|
Tribouilloy|Christophe|C|
Maréchaux|Sylvestre|S|

Longitudinal strain
Speckle tracking
Echocardiography
Strain longitudinal
Échocardiographie


Toward immunosuppressive effects on liver transplantation in rat model: tacrolimus loaded poly(ethylene glycol)-poly(D,L-lactide) nanoparticle with longer survival time.

Abstract: In this study, tacrolimus (FK506) was encapsulated into a biodegradable poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA) block copolymer using a double emulsion-solvent evaporation technique. Drug loading (DL) and encapsulation efficiency (EE) can be changed by varying the mass ratio of FK506/MPEG-PLA. Furthermore, transmission electron microscope (TEM) and Malvern Zetasizer were used to investigate the properties of FK506/MPEG-PLA nanoparticles (DL=9.5%), which were monodisperse (PDI=0.100 ± 0.023) with a mean particle size of 90.5 ± 1.5 nm. Compared with FK506 capsule, in vitro release profile showed that FK506/MPEG-PLA nanoparticles exhibited sustained release. Meanwhile, the higher concentration and longer retention time in plasma were also confirmed in vivo. We further preliminarily evaluated immunosuppressive effect on liver transplantation in rat model. The survival time of the rat administrated FK506/MPEG-PLA nanoparticles was obviously prolonged than that of the control group administrated FK506 capsule.

Immunosuppressive
Liver transplantation
Tacrolimus
Nanoparticle
MPEG-PLA


Diet-induced obesity and kidney disease - In search of a susceptible mouse model.

Abstract: Obesity and metabolic syndrome are independent risk factors for chronic kidney disease, even without diabetes or hyperglycemia. Here, we compare two mouse models that are susceptible to diet-induced obesity: the relatively renal injury resistant C57BL/6J strain and the DBA2/J strain which is more sensitive to renal injury. Our studies focused on characterizing the effects of high fat diet feeding on renal oxidative stress, albuminuria, fibrosis and podocyte loss/insulin resistance. While the C57BL/6J strain does not develop significant pathological changes in the kidney, at least on lard based diets within the time frame investigated, it does show increased renal iNOS and nitrotyrosine levels and elevated mitochondrial respiration which may be indicative of mitochondrial lipid overfueling. Restricting the high fat diet to decrease adiposity decreased the levels of cellular oxidative stress markers, indicating that adiposity-related proinflammatory changes such as increased iNOS levels may trigger similar responses in the kidney. Mitochondrial respiration remained higher, suggesting that eating excess lipids, despite normal adiposity may still lead to renal mitochondrial overfueling. In comparison, DBA/2J mice developed albuminuria on similar diets, signs of fibrosis, oxidative stress, early signs of podocyte loss (evaluated by the markers podocin and WT-1) and podocyte insulin resistance (unable to phosphorylate their glomerular Akt when insulin was given). To summarize, while the C57BL/6J strain is not particularly susceptible to renal disease, changes in its mitochondrial lipid handling combined with the easy availability of transgenic technology may be an advantage to design new knockout models related to mitochondrial lipid metabolism. The DBA/2J model could serve as a basis for studying podocyte insulin resistance and identifying early renal markers in obesity before more severe kidney disease develops. Based on our observations, we encourage further critical evaluation of mouse models for obesity related chronic kidney disease.

Wicks|Shawna E|SE|
Nguyen|Trang-Tiffany|TT|
Breaux|Chelsea|C|
Kruger|Claudia|C|
Stadler|Krisztian|K|

Obesity
Mouse models
Chronic kidney disease
High fat diet
Oxidative stress


Interactions between sleep disruption, motor learning, and p70 S6 kinase 1 signaling.

Abstract: Offline gains in motor performance after initial motor learning likely depend on sleep, but the molecular mechanisms by which this occurs are understudied. Regulation of mRNA translation via p70 S6 kinase 1 (S6K1) signaling represents one potential mechanism, as protein synthesis is thought to be increased during sleep compared to wake and is necessary for several forms of long-term memory. Using phosphorylation of ribosomal protein S6 (RpS6) as a readout of S6K1 activity, we demonstrate that a period of 10 h of acute sleep disruption impairs both S6K1 signaling and offline gains in motor performance on the rotarod in adult wild type C57/Bl6 mice. Rotarod motor learning results in increased abundance of RpS6 in the striatum, and inhibition of S6K1 either indirectly with rapamycin or directly with PF-4708671 diminished the offline improvement in motor performance without affecting the initial acquisition of rotarod motor learning when sleep is normal. In sum, S6K1 activity is required for sleep-dependent offline gains in motor performance and is inhibited following acute sleep disruption, while motor learning increases the abundance of striatal RpS6. Thus, S6K1 signaling represents a plausible mechanism mediating the beneficial effects of sleep on motor performance.

Kam|Korey|K|
Kang|Mihwa|M|
Eren|C Yasemin|CY|
Pettibone|Ward D|WD|
Bowling|Heather|H|
Taveras|Shantal|S|
Ly|Annie|A|
Chen|Rebecca K|RK|
Berryman|Natasha V|NV|
Klann|Eric|E|
Varga|Andrew W|AW|

D038762:Ribosomal Protein S6 Kinases, 70-kDa

mRNA translation
protein synthesis
ribosomal protein S6
rotarod
rapamycin
PF-4708671
mTORC1


Metastatic Patterns of Solitary Fibrous Tumors: A Single-Institution Experience.

Abstract:
OBJECTIVE
The objective of our study was to evaluate the metastatic patterns and imaging features of solitary fibrous tumors (SFTs).

MATERIALS AND METHODS
This retrospective study included 139 patients with pathologically proven SFT, 49 of whom developed metastases. Electronic medical records and all available images were reviewed to record the pattern and imaging appearances of metastatic disease, and comparisons of thoracic SFTs and extrathoracic SFTs were also performed. Associations of metastatic spread were studied using univariate and multivariate Cox regression analyses.

RESULTS
A total of 49 (35%) patients developed metastases at a median of 124 months (interquartile range [IQR], 66-195 months) after SFT diagnosis; 11 patients (8%) had metastases at presentation. Of these 49 patients, 40 patients died at a mean of 183 months after diagnosis. The associations with metastatic disease on univariate analysis were tumor size ≥ 10 cm (p = 0.01) and malignant pathology or mitotic count ≥ 4 per 10 high-power fields (HPF) (p < 0.001). Malignant pathology and a mitotic count of ≥ 4 per 10 HPF were also associated with metastatic disease on multivariate analysis (p = 0.01; hazard ratio, 0.22; 95% CI, 0.05-0.73). The most common sites of metastasis were the lungs (30/49, 61%) followed by the pleura (24/49, 49%) and then the liver (20/49, 41%), bones (20/49, 41%), and peritoneum (20/49, 41%). A significantly higher proportion of patients with extrathoracic SFT had metastatic disease (37/139, 27%) compared with those with thoracic SFT (12/139, 9%) (p = 0.003). The overall metastasis-free survival was a median of 117 months (IQR, 33-169 months) in patients with extrathoracic SFT and a median of 120 months (IQR, 82-169 months) in patients with thoracic SFT (p = 0.01).

CONCLUSION
A mitotic count of ≥ 4 per 10 HPF or malignant pathology was significantly associated with metastatic disease on both univariate and multivariate analyses. The sites of metastatic disease differed depending on the site of the primary SFT but were most commonly the lung and pleura. Patients with extrathoracic SFT were statistically more likely to develop metastatic disease than those with thoracic SFT.

O'Neill|Ailbhe C|AC|
Tirumani|Sree Harsha|SH|
Do|Woo S|WS|
Keraliya|Abhishek R|AR|
Hornick|Jason L|JL|
Shinagare|Atul B|AB|
Ramaiya|Nikhil H|NH|

solitary fibrous tumor
metastases
thoracic
extrathoracic


The effect of bee prepolis on primary dysmenorrhea: a randomized clinical trial.

Abstract:
Objective
Primary dysmenorrhea typically occurs with no associated pelvic pathology and is common in adolescents and young women. This study evaluated the effect of bee propolis on relief of primary dysmenorrhea.

Methods
The study was performed in 2018 in Hamadan, in western Iran, among female students with primary dysmenorrhea. Participants were randomly divided into two groups, using balanced block randomization, and were administered a placebo or bee propolis capsules for 5 days during two menstruation cycles. The number of participants required was estimated to be 86 in total, with 43 students in each group according to the inclusion criteria. We used the visual analog scale to assess pain severity. The independent t-test was conducted for comparing between two groups, using SPSS 16.0.

Results
A significant change was found in the mean pain scores during the first (P<0.001) and second (P<0.001) months after using bee propolis in comparison with placebo. The means of the pain scores in the bee propolis group were 5.32±2.28 and 4.74±2.40 in first and second months after the intervention, respectively, whereas the means of the pain scores in the placebo group were 7.40±1.21 and 7.17±1.24 in first and second months after the intervention, respectively.

Conclusion
Our study showed that the use of bee propolis for two months compared with placebo reduced primary dysmenorrhea during the first and second months after use, with no adverse effects. Therefore, it could be used as an alternative to nonsteroidal anti-inflammatory drugs for relief of primary dysmenorrhea.

Primary dysmenorrhea
Adolescent
Bee propolis


Assessment of older adults' decision-making capacity in relation to independent living: A scoping review.

Abstract: With a growing global ageing population, approaches to assess and support decision-making are becoming more pertinent. This scoping review aimed to identify and map current knowledge on assessment of older adults' decision-making capacity in relation to independent living. A five-stage scoping review framework was followed. Inclusion criteria were papers on assessment approaches used to evaluate decision-making capacity of older adults, aged 60 years and over for independent living, including studies involving people with cognitive impairment and dementia. Five databases were searched for publications with eligibility criteria from January 2000 to December 2020; 4,118 results were retrieved from sources, resulting in 29 publications being analysed, eight of which were research reports. Publication characteristics and methodologies varied; however, many common components of decision-making capacity assessment for independent living were identified including cognitive, functional, environmental and risk assessment. Overall, a multidisciplinary approach was recommended, and consideration of the person's values and preferences is noted in many publications. Decision-making capacity assessment for independent living of older adults requires multicomponent, multidisciplinary assessment. Future work is needed to examine this from the perspective of older adults and their caregivers.

older adults
decision-making capacity
independent living
scoping review


Vincristine as an Adjunct to Therapeutic Plasma Exchange for Thrombotic Thrombocytopenic Purpura: A Single-Institution Experience

Abstract:
Background
Thrombotic thrombocytopenic purpura is a potentially life-threatening condition. Although the introduction of therapeutic plasma exchange has reduced mortality rates from over 90% to 10%-20%, approximately 40% of patients relapse, and outcomes may be fatal in refractory patients. There is clearly a need for additional therapeutic approaches.

Aims
To describe the outcomes of relapsed/refractory thrombotic thrombocytopenic purpura patients treated with vincristine as an adjunct to therapeutic plasma exchange.

Study Design
Cross-sectional study.

Methods
The medical records of all relapsed/refractory patients with thrombotic thrombocytopenic purpura treated with vincristine adjunct to therapeutic plasma exchange between October 2000 and December 2016 were retrospectively reviewed. Diagnosis of thrombotic thrombocytopenic purpura was based on clinical history, physical examination, and laboratory examinations. Patient demographics, laboratory findings, initial date and duration of therapeutic plasma exchange, dosage and time of administration of vincristine, and outcomes were recorded.

Results
The study included 15 patients [median age: 37 years (range: 26-65); 7 women and 8 men] with either relapsed or refractory thrombotic thrombocytopenic purpura who were treated with vincristine as an adjunct to therapeutic plasma exchange for a total of 22 episodes. Eighty-seven percent of patients achieved remissions in 20 of 22 episodes, with a median duration of remission of 29.5 months (range: 3-105). After a median follow-up of 55 months, 11 patients were alive. Vincristine was well tolerated with no safety concerns.

Conclusion
Vincristine offers a reasonable option for the treatment of patients with relapsed/refractory thrombotic thrombocytopenic purpura. Further studies evaluating vincristine in the front-line setting and in the relapsed/refractory setting are needed to validate the role of vincristine in thrombotic thrombocytopenic purpura patients.

Öngören|Seniz|S|
Salihoğlu|Ayşe|A|
Apaydın|Tuğçe|T|
Sadri|Sevil|S|
Eşkazan|Ahmet Emre|AE|
Ar|Muhlis Cem|MC|
Elverdi|Tuğrul|T|
Başlar|Zafer|Z|
Aydın|Yıldız|Y|
Soysal|Teoman|T|

vincristine
Plasma exchange
thrombotic thrombocytopenic
purpura


Efficacy of halofuginone lactate against experimental cryptosporidiosis in goat neonates.

Abstract: Preliminary results obtained in calves, lambs and goat kids infected by Cryptosporidium sp. have indicated a partial prophylactic efficacy of halofuginone lactate when administered at 100 μg/kg body weight (BW). In this study, the efficacy of halofuginone lactate was evaluated in goat neonates experimentally inoculated with Cryptosporidium parvum oocysts per oral route. The trial consisted in 2 replicated experiments carried out successively at 2 months of interval. Twenty-two 2- to 4-day-old kids were experimentally inoculated once, 2-3 days after the arrival in premises, with 10(6)C. parvum oocysts per oral route and were allocated into 2 groups. Animals of group 1 acted as untreated control whereas animals of group 2 received halofuginone lactate for 10 days from the infection day to day 9 post-infection (DPI) at a daily oral dose rate of 100 μg/kg BW. Individual oocyst shedding was monitored by daily examination of faecal smears stained by carbol fuchsin and scored semi-quantitatively (0-5) until 19 DPI. Daily diarrhoea scores, weight gain and mortality were recorded. In the first experiment, oocyst excretion started 1 DPI in the control group, was highest on 4 DPI (mean score 3.6) and became undetectable from 16-19 DPI. In the treated group, oocyst shedding started 1 day later, showed lower scores compared to control on 4, 5, 6, 7 and 10 DPI and vanished from 16 to 19 DPI. No significant difference was seen for weight gains between groups. Five kids died in the control group compared to 1 kid in the treated group. In the second (replicated) experiment, oocyst excretion started 2 DPI in the control group, was highest on 4 DPI (mean score 4.5) and became undetectable 18 and 19 DPI. In the treated group, oocyst shedding started 2 days later, peaked on 13 DPI (mean score 2.3) and persisted until the end of the experiment. No significant difference was seen for weight gains between groups. Ten kids died in the control group compared to 3 kids in the treated group. The results demonstrated the efficacy of halofuginone lactate when given as a prophylactic treatment at 100 μg/kg BW during 10 days in reducing oocyst shedding, diarrhoea and mortality in goat kid cryptosporidiosis.

Petermann|Julie|J| Paraud|Carine|C| Pors|Isabelle|I| Chartier|Christophe|C|

Halofuginone lactate
Cryptosporidium parvum
Control methods-protozoa
Goat-protozoa


A Review of Brain Stimulation Treatments for Late-Life Depression.

Abstract: Opinion Statement Recurrence, relapse and resistance to first-line therapies are common and pervasive issues in the treatment of depression in older adults. As a result, brain stimulation modalities are essential treatment options in this population. The majority of data for the effectiveness of brain stimulation modalities comes from electroconvulsive therapy (ECT) studies. Current ECT trials are focused on prolonging response after a successful course and mitigating the cognitive adverse effects. Newer forms of brain stimulation have emerged; unfortunately, as with most advances in medicine older adults have not been systematically included in clinical trials. Repetitive transcranial magnetic stimulation has demonstrated efficacy in younger adults and there is emerging data to support its use in late-life depression (LLD). It will be imperative that older adults be included in future transcranial direct current stimulation and magnetic seizure therapy clinical trials. Unclear efficacy results are a concern for both vagus nerve stimulation and deep brain stimulation.

Blumberger|Daniel M|DM|
Hsu|Jonathan H|JH|
Daskalakis|Zafiris J|ZJ|

Repetitive transcranial magnetic simulation


Total Ischemic Event Reduction With Rivaroxaban After Peripheral Arterial Revascularization in the VOYAGER PAD Trial.

Abstract:
BACKGROUND
Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events. The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population is unknown.

OBJECTIVES
This study sought to evaluate the total burden of vascular events in patients with PAD after LER and the efficacy of low-dose rivaroxaban on total events.

METHODS
VOYAGER PAD randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone. The primary endpoint was time to first event of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The current analysis considered all events (first and subsequent) for components of the primary endpoint as well as additional vascular events including peripheral revascularizations and venous thromboembolism. HRs were estimated by marginal proportional hazards models.

RESULTS
Among 6,564 randomized events, there were 4,714 total first and subsequent vascular events including 1,614 primary endpoint events and 3,100 other vascular events. Rivaroxaban reduced total primary endpoint events (HR: 0.86; 95% CI: 0.75-0.98; P = 0.02) and total vascular events (HR: 0.86; 95% CI: 0.79-0.95; P = 0.003). An estimated 4.4 primary and 12.5 vascular events per 100 participants were avoided with rivaroxaban over 3 years.

CONCLUSIONS
Patients with symptomatic PAD who are undergoing LER have a high total event burden that is significantly reduced with rivaroxaban. Total event reduction may be a useful metric to quantify the efficacy of rivaroxaban in this setting. (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities [VOYAGER PAD]; NCT02504216).

Bauersachs|Rupert M|RM|
Szarek|Michael|M|
Brodmann|Marianne|M|
Gudz|Ivan|I|
Debus|Eike Sebastian|ES|
Nehler|Mark R|MR|
Anand|Sonia S|SS|
Patel|Manesh R|MR|
Hess|Connie N|CN|
Capell|Warren H|WH|
Rogers|Kevin|K|
Muehlhofer|Eva|E|
Haskell|Lloyd P|LP|
Berkowitz|Scott D|SD|
Hiatt|William R|WR|
Bonaca|Marc P|MP|
|||

rivaroxaban
revascularization
peripheral artery disease
acute limb ischemia


Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes.

Abstract: Rodent-based studies have shown that the membrane properties of oligodendrocytes play prominent roles in their physiology and shift markedly during their maturation from the oligodendrocyte precursor cell (OPC) stage. However, the conservation of these properties and maturation processes in human oligodendrocytes remains unknown, despite their dysfunction being implicated in human neurodegenerative diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Here, we have defined the membrane properties of human oligodendrocytes derived from pluripotent stem cells as they mature from the OPC stage, and have identified strong conservation of maturation-specific physiological characteristics reported in rodent systems. We find that as human oligodendrocytes develop and express maturation markers, they exhibit a progressive decrease in voltage-gated sodium and potassium channels and a loss of tetrodotoxin-sensitive spiking activity. Concomitant with this is an increase in inwardly rectifying potassium channel activity, as well as a characteristic switch in AMPA receptor composition. All these steps mirror the developmental trajectory observed in rodent systems. Oligodendrocytes derived from mutant C9ORF72-carryng ALS patient induced pluripotent stem cells did not exhibit impairment to maturation and maintain viability with respect to control lines despite the presence of RNA foci, suggesting that maturation defects may not be a primary feature of this mutation. Thus, we have established that the development of human oligodendroglia membrane properties closely resemble those found in rodent cells and have generated a platform to enable the impact of human neurodegenerative disease-causing mutations on oligodendrocyte maturation to be studied.

Livesey|Matthew R|MR|
Magnani|Dario|D|
Cleary|Elaine M|EM|
Vasistha|Navneet A|NA|
James|Owain T|OT|
Selvaraj|Bhuvaneish T|BT|
Burr|Karen|K|
Story|David|D|
Shaw|Christopher E|CE|
Kind|Peter C|PC|
Hardingham|Giles E|GE|
Wyllie|David J A|DJ|
Chandran|Siddharthan|S|

Electrophysiology
Human
Oligodendrocyte
oligodendrocyte precursor cell
Amyotrophic lateral sclerosis
Stem cell


Bayesian inference reveals ancient origin of simian foamy virus in orangutans.

Abstract: Simian foamy viruses (SFVs) infect most nonhuman primate species and appears to co-evolve with its hosts. This co-evolutionary signal is particularly strong among great apes, including orangutans (genus Pongo). Previous studies have identified three distinct orangutan SFV clades. The first of these three clades is composed of SFV from P. abelii from Sumatra, the second consists of SFV from P. pygmaeus from Borneo, while the third clade is mixed, comprising an SFV strain found in both species of orangutan. The existence of the mixed clade has been attributed to an expansion of P. pygmaeus into Sumatra following the Mount Toba super-volcanic eruption about 73,000years ago. Divergence dating, however, has yet to be performed to establish a temporal association with the Toba eruption. Here, we use a Bayesian framework and a relaxed molecular clock model with fossil calibrations to test the Toba hypothesis and to gain a more complete understanding of the evolutionary history of orangutan SFV. As with previous studies, our results show a similar three-clade orangutan SFV phylogeny, along with strong statistical support for SFV-host co-evolution in orangutans. Using Bayesian inference, we date the origin of orangutan SFV to >4.7 million years ago (mya), while the mixed species clade dates to approximately 1.7mya, >1.6 million years older than the Toba super-eruption. These results, combined with fossil and paleogeographic evidence, suggest that the origin of SFV in Sumatran and Bornean orangutans, including the mixed species clade, likely occurred on the mainland of Indo-China during the Late Pliocene and Calabrian stage of the Pleistocene, respectively.

Reid|Michael J C|MJC|
Switzer|William M|WM|
Schillaci|Michael A|MA|
Klegarth|Amy R|AR|
Campbell|Ellsworth|E|
Ragonnet-Cronin|Manon|M|
Joanisse|Isabelle|I|
Caminiti|Kyna|K|
Lowenberger|Carl A|CA|
Galdikas|Birute Mary F|BMF|
Hollocher|Hope|H|
Sandstrom|Paul A|PA|
Brooks|James I|JI|

D000818:Animals
D001499:Bayes Theorem
D000073930:Biological Coevolution
D001893:Borneo
D004272:DNA, Mitochondrial
D003576:Electron Transport Complex IV
D005580:Fossils
D015870:Gene Expression
D005814:Genes, Viral
D016679:Genome, Viral
D049690:History, Ancient
D054884:Host-Pathogen Interactions
D007214:Indonesia
D057079:Pongo
D012192:Retroviridae Infections
D053150:Simian foamy virus
D018707:Volcanic Eruptions

Orangutans
SFV
Pongo
Co-evolution
Mt. Toba
Paleobiogeography
Paleovirology


Natural Gas Gathering and Transmission Pipelines and Social Vulnerability in the United States.

Abstract: Midstream oil and gas infrastructure comprises vast networks of gathering and transmission pipelines that connect upstream extraction to downstream consumption. In the United States (US), public policies and corporate decisions have prompted a wave of proposals for new gathering and transmission pipelines in recent years, raising the question: Who bears the burdens associated with the existing pipeline infrastructure in the US? With this in mind, we examined the density of natural gas gathering and transmission pipelines in the US, together with county-level data on social vulnerability. For the 2,261 US counties containing natural gas pipelines, we found a positive correlation between county-level pipeline density and an index of social vulnerability. In general, counties with more socially vulnerable populations have significantly higher pipeline densities than counties with less socially vulnerable populations. In particular, counties in the top quartile of social vulnerability tend to have pipeline densities that are much higher than pipeline densities for counties in the bottom quartile of social vulnerability. The difference grows larger for counties at the upper extremes of pipeline density within each group. We discuss some of the implications for the indigenous communities and others affected by recent expansions of oil and gas infrastructure. We offer recommendations aimed at improving ways in which decision-makers identify and address the societal impacts and environmental justice implications of midstream pipeline infrastructure.

infrastructure
environmental justice
complex systems
energy
indigenous peoples


Impact of comorbid polycystic ovarian syndrome and gestational diabetes mellitus on pregnancy outcomes: a retrospective cohort study.

Abstract:
BACKGROUND
Gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS) have been associated with adverse maternal and neonatal outcomes, but the evidence on the impact of coexistent PCOS and GDM is rather limited and inconclusive. We investigated the impact of comorbid PCOS on pregnancy outcomes among women with GDM.

METHODS
This retrospective cohort study included women diagnosed with GDM on 75 g oral glucose tolerance test on routine antenatal screening tests at Liverpool Hospital between February 2015 and January 2019. Women were then grouped into those with and without PCOS based on the Rotterdam criteria. The demographic details, clinical data and pregnancy outcomes were compared between the two groups.

RESULTS
Among the 1545 women with GDM included in the study, there were 326 women with PCOS. Women with GDM and PCOS (GDM+PCOS+) were younger (29.5 years vs 31.5 years, p < 0.001), more likely to be primigravidae (31.9% vs 20%, p < 0.001), as well as of Caucasian descent (37.4% vs 21.7%, p < 0.001). PCOS was an independent risk factor for the development of preeclampsia on regression analysis (OR 2.06, p = 0.021). Women with PCOS and GDM had a higher body mass index (31.5 kg/m2 vs 27.7 kg/m2, p < 0.001), significant gestational weight gain (12.6 kg vs 11.5 kg, p = 0.016), and more frequent use of pharmacotherapies to manage their GDM (57.7% vs 45.2%, p < 0.001). There was no statistically significant difference in the rates of adverse neonatal outcomes in both the groups.

CONCLUSION
Among women with GDM, PCOS was an independent risk factor for the development of preeclampsia and significant gestational weight gain, warranting vigilant monitoring of blood pressure, blood glucose levels and body weight, and implementing timely interventions to improve obstetric and neonatal outcomes.

Polycystic ovarian syndrome
Gestational diabetes mellitus
Pregnancy
Outcomes
Complications


Similarity Calculation, Enrichment Analysis, and Ontology Visualization of Biomedical Ontologies using UFO.

Abstract: The rapid growth of biomedical ontologies observed in recent years has been reported to be useful in various applications. In this article, we propose two main-function protocols-term-related and entity-related-with the three most common ontology analyses, including similarity calculation, enrichment analysis, and ontology visualization, which can be done by separate methods. Many previously developed tools implementing those methods run on different platforms and implement a limited number of the methods for similarity calculation and enrichment analysis tools for a specific type of biomedical ontology, although any type can be acceptable. Moreover, depending on each application, methods have distinct advantages; thus, the greater the number of methods a tool has, the better decisions that users make. The protocol here implements all the analyses above using an advanced popular tool called UFO. UFO is a Cytoscape app that unifies most of the semantic similarity measures for between-term and between-entity similarity calculation for biomedical ontologies in OBO format, which can calculate the similarity between two sets of entities and weigh imported entity networks, as well as generate functional similarity networks. The complete protocol can be performed in 30 min and is designed for use by biologists with no prior bioinformatics training. © 2021 Wiley Periodicals LLC. Basic Protocol: Running UFO using a list of input Gene Ontology, Disease Ontology, or Human Phenotype Ontology data.

D064229:Biological Ontologies
D019295:Computational Biology
D003955:Diagnostic Tests, Routine
D063990:Gene Ontology
D006801:Humans
D012660:Semantics

similarity calculation
enrichment analysis
ontology
ontology visualization
Cytoscape App


The Cutting Edge: The Role of mTOR Signaling in Laminopathies.

Abstract: The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase that regulates anabolic and catabolic processes, in response to environmental inputs. The existence of mTOR in numerous cell compartments explains its specific ability to sense stress, execute growth signals, and regulate autophagy. mTOR signaling deregulation is closely related to aging and age-related disorders, among which progeroid laminopathies represent genetically characterized clinical entities with well-defined phenotypes. These diseases are caused by LMNA mutations and feature altered bone turnover, metabolic dysregulation, and mild to severe segmental progeria. Different LMNA mutations cause muscular, adipose tissue and nerve pathologies in the absence of major systemic involvement. This review explores recent advances on mTOR involvement in progeroid and tissue-specific laminopathies. Indeed, hyper-activation of protein kinase B (AKT)/mTOR signaling has been demonstrated in muscular laminopathies, and rescue of mTOR-regulated pathways increases lifespan in animal models of Emery-Dreifuss muscular dystrophy. Further, rapamycin, the best known mTOR inhibitor, has been used to elicit autophagy and degradation of mutated lamin A or progerin in progeroid cells. This review focuses on mTOR-dependent pathogenetic events identified in Emery-Dreifuss muscular dystrophy, LMNA-related cardiomyopathies, Hutchinson-Gilford Progeria, mandibuloacral dysplasia, and type 2 familial partial lipodystrophy. Pharmacological application of mTOR inhibitors in view of therapeutic strategies is also discussed.

Emery-Dreifuss muscular dystrophy (EDMD)

Hutchinson-Gilford progeria syndrome (HGPS)


Periprosthetic fractures after total knee arthroplasty.

Abstract:
PURPOSE
To evaluate outcome in 20 patients treated for periprosthetic fractures after total knee arthroplasty (TKA).

METHODS
Records of 14 women and 6 men aged 45 to 85 (mean, 67) years who underwent operative (n=18) or conservative (n=2) treatment for periprosthetic fractures of the supracondylar femur (n=15), patella (n=3), and tibia (n=2) following minor falls (n=18) or high-velocity injury (n=2) were reviewed. The mean time from TKA to fracture was 43 (range, 14-98) months. Of the 15 supracondylar femoral fractures, 2 were managed with immobilisation in a long leg cast, 11 with internal fixation using locked compression plating, and 2 with revision arthroplasty. All 3 patellar fractures were managed with tension band wiring. Both tibial fractures were managed with revision arthroplasty. Radiographic and functional outcomes (the Knee Society scores) were assessed.

RESULTS
The mean follow-up was 35 (range, 24-48) months. All fractures healed after a mean of 15 (range, 12-38) weeks. One patient had delayed union. Postoperative alignment was satisfactory in all patients except one (with 5º varus). The mean tibiofemoral angle was 4º valgus. The mean range of motion was 98.5º. The mean Knee Society knee score was 85 (range, 75-89) and the functional score was 76 (range, 70-85). No patient had implant failure, loss of reduction, deep infection, deep vein thrombosis, or pulmonary embolism.

CONCLUSION
The locked compression plate is effective in managing periprosthetic femoral fractures. Periprosthetic patellar and tibial fractures are uncommon. The latter often warrant revision arthroplasty owing to the loose implant.

Agarwal|Saurabh|S|
Sharma|Rajeev K|RK|
Jain|Jitesh Kumar|JK|

D000368:Aged
D000369:Aged, 80 and over
D019645:Arthroplasty, Replacement, Knee
D005260:Female
D005264:Femoral Fractures
D005500:Follow-Up Studies
D005593:Fracture Fixation, Internal
D017102:Fracture Healing
D006801:Humans
D016268:Internal Fixators
D007719:Knee Joint
D008297:Male
D008875:Middle Aged
D057068:Periprosthetic Fractures
D011475:Prosthesis Failure
D011859:Radiography
D016059:Range of Motion, Articular
D012189:Retrospective Studies
D013978:Tibial Fractures
D016896:Treatment Outcome

periprosthetic fractures
arthroplasty, replacement, knee


Sex-pairing pheromone of Ancistrotermes dimorphus (Isoptera: Macrotermitinae).

Abstract: Ancistrotermes dimorphus is a common Macrotermitinae representative, facultative inquiline by its life-style, occurring in South-East China. Sex pheromone is used for couple formation and maintenance, and it is produced by and released from the female sternal gland and is highly attractive to males. Based on our combined behavioral, chemical and electrophysiological analyses, we identified (3Z,6Z)-dodeca-3,6-dien-1-ol as the female sex pheromone of A. dimorphus as it evoked the tandem behavior at short distance, and the active quantities ranged from 0.01ng to 10ng. Interestingly, GC-MS analyses of SPME extracts showed another compound specific to the female sternal gland, (3Z)-dodec-3-en-1-ol, which showed a clear GC-EAD response. However, this compound has no behavioral function in natural concentrations (0.1ng), while higher amounts (1ng) inhibit the attraction achieved by (3Z,6Z)-dodeca-3,6-dien-1-ol. The function of (3Z)-dodec-3-en-1-ol is not fully understood, but might be linked to recognition from sympatric species using the same major compound, enhancing the long-distance attraction, or informing about presence of other colonies using the compound as a trail-following pheromone. The sternal gland secretion of Ancistrotermes females contains additional candidate compounds, namely (3E,6Z)-dodeca-3,6-dien-1-ol and (6Z)-dodec-6-en-1-ol, which are not perceived by males' antennae in biologically relevant amounts.

Wen|Ping|P| Mo|Jianchu|J| Lu|Chunwen|C| Tan|Ken|K| Šobotník|Jan|J| Sillam-Dussès|David|D|


Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment.

Abstract:
OBJECTIVE
To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease-modifying treatments (DMT).

METHOD
The Registry created in 2008 included patients of eight centers. All available data in 2008 were retrospectively encoded in the database. After 2008 and until 2012, all data were recorded prospectively for already registered patients as well as newly diagnosed subjects. Data were registered from neonatal screening or from diagnosis (first contact) until last follow-up or death. Data included diagnosis, demography, and outcome data.

RESULTS
We collected data from 469 patients over a 5,110 patient years (PY) follow-up period. The global mortality rate was low (0.25/100 PY), although 13 patients died (2.8%) and was similar between children, adolescents (10-18 years), and young adults (P = 0.76). Out of the cohort, 185 patients received hydroxyurea at last follow-up (median duration of treatment: 10.3 years), 90 underwent hematopoietic stem cell transplantation (HSCT), 24 were chronically transfused, and 170 had never had any DMT. Hydroxyurea showed significant benefit on patients outcome as reflected by a lower mortality rate compared to transplanted individuals or people without DMT (0.14, 0.36, and 0.38 per 100 PY, respectively) and by higher Kaplan-Meier estimates of 15 year survival (99.4%) compared to HSCT (93.8%; P = 0.01) or no DMT groups (95.4%; P = 0.04).

CONCLUSION
SCD mortality in Belgium is low with no increase observed in young adults. Patients treated with hydroxyurea demonstrate a significant benefit in survival when compared to those without DMT or transplanted.

Lê|Phu Quoc|PQ|
Gulbis|Béatrice|B|
Dedeken|Laurence|L|
Dupont|Sophie|S|
Vanderfaeillie|Anna|A|
Heijmans|Catherine|C|
Huybrechts|Sophie|S|
Devalck|Christine|C|
Efira|André|A|
Dresse|Marie-Françoise|MF|
Rozen|Laurence|L|
Benghiat|Fleur Samantha|FS|
Ferster|Alina|A|

D018380:Hematopoietic Stem Cell Transplantation

survival
sickle cell disease
hydroxyurea
mortality


Phylogenetic and pathogenic analysis of Mycoplasma Synoviae isolated from native chicken breeds in China.

Abstract: Mycoplasma synoviae (M. synoviae) infection leads to serious economic losses in the world every year. Between 2013 and 2014, the infectious synovitis, caused by M. synoviae infection, occurred in native chickens in China and resulted in the loss of millions of chickens in Chinese poultry farms. However, there has been no data about phylogenetic and pathogenic analysis of Chinese M. synoviae isolates. In this study, a total of 110 M. synoviae strains were isolated from M. synoviae infected chickens. The isolates identified in the present study were classified into a new distinct subgroup based on analysis of the 5'-end vlhA sequences, tentatively termed the K group. In addition, though the pathogenicity was significantly different among isolates, there was no close relationship between pathogenicity and genotype for Chinese M. synoviae based on a pathogenic analysis of the 5'-end of the vlhA gene.

Sun|Shikai|S| Lin|Xin|X| Liu|Junmei|J| Tian|Zhongqiang|Z| Chen|Feng|F| Cao|Yongchang|Y| Qin|Jianping|J| Luo|Tingrong|T|

pathogenicity
Mycoplasma synoviae
vlhA
Chinese native chicken breeds
phylogenetic analysis


Trends in PCI volume after negative results from the COURAGE trial.

Abstract:
OBJECTIVE
To describe trends in the use of percutaneous coronary intervention (PCI) following the COURAGE trial, which found that medical therapy is as effective as PCI for patients with stable angina.

DATA SOURCES
We used the National Hospital Discharge Survey; inpatient and outpatient discharge data from Florida, Maryland, and New Jersey; and the English Hospital Episode Statistics database.

STUDY DESIGN
We report trends in PCI volume by diagnosis (stable angina vs. unstable angina or AMI) before and after publication of the COURAGE trial.

PRINCIPAL FINDINGS
The number of PCIs in patients without a diagnosis of AMI or unstable angina in Florida, Maryland, and New Jersey declined from 48,000 in 2006 to 40,000 in 2008 (-17 percent). There was no change in the number of PCIs in patients with a diagnosis of AMI. We observed similar patterns in U.S. community hospitals. PCI volume did not decline in England.

CONCLUSIONS
PCI volume declined after publication of the COURAGE trial. The experience of the COURAGE trial suggests that comparative effectiveness research can lead to cost-saving changes in medical practice patterns. However, there are many patients with stable coronary disease who continue to receive PCI post-COURAGE.

D016032:Randomized Controlled Trials as Topic

use
Medical decision making
access
demand
diffusion
technology adoption
utilization of services


Relationship of clinical measures with humeral torsion in young adults: a pilot study.

Abstract:
PURPOSE
Humeral retroversion alters range of motion and has been linked to injury risk. Clinically,palpation of the bicipital groove is used to quantify humeral torsion, but the accuracy of this procedure has not been fully examined. The purpose of this study was to investigate the relationship between clinical and diagnostic ultrasound (US) assessment of humeral torsion while considering shoulder position of the participant and clinical expertise of the examiner.

METHODS
Seventeen participants (34 shoulders, 16/17 right handed, 10/17 history of throwing) were recruited. US was assessed by an experienced assessor. Two clinical assessments of humeral torsion were performed by two assessors of different experience (expert and novice). Humeral torsion was assessed at 90 degrees shoulder abduction (Palp90) and 45 degrees shoulder abduction (Palp45). Within assessor intraclass correlation coefficients (ICC (3, 1) were calculated. Correlation coefficients (Pearson's) were generated to determine relationship between clinical and US examination findings.

RESULTS
Intra-rater reliability for clinical tests were good (ICCs .73 - .92) for both raters. Of the palpation tests, only the expert assessor was significantly correlated to the US measurement (p<.001) at Palp45 (r = .64) and Palp90 (r = .62). For the expert, there was a significantly lower angle calculated for Palp45 compared to Palp90 (p<.001).

CONCLUSION
The accuracy of both palpation methods for assessing humeral retrotorsion may depend on the training background of the assessor. Further, the glenohumeral position of the patient during palpation should be consistent for the purposes of repeated testing.

Werner|David M|DM|
Bellm|Eric V|EV|
Day|Joseph M|JM|

palpation
Ultrasound
shoulder
manual therapy
overhead athlete


Impact of N-Truncated Aβ Peptides on Cu- and Cu(Aβ)-Generated ROS: CuI Matters!

Abstract: In vitro Cu(Aβ1-x )-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of Aβ to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (Aβ4-x and Aβ11-x ) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2 N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aβ1-x peptide. It has further been proposed that the role of Aβ4-x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII , CuI coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (CuI and CuII ) complexes of the Aβ4-16 and Aβ11-16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ1-16 ), the N-truncated peptides are not able to fully preclude Cu(Aβ1-16 )-induced ROS production.

D016229:Amyloid beta-Peptides
D003300:Copper
D006801:Humans
D010446:Peptide Fragments
D058225:Plaque, Amyloid
D017382:Reactive Oxygen Species

copper
amyloid beta-peptides
bioinorganic chemistry
chelates
reactive oxygen species


Incidental intra-operative finding of a rare uterine fusion abnormality in a primigravida with breech presentation at term: A case report.

Abstract: Uterine malformations are often asymptomatic but can be associated with a wide range of reproductive problems. We report a case of uterine fusion defect diagnosed intra-operatively in a 20-year-old primigravida who had elective caesarean section at term on account of breech presentation at term. Intraoperative findings included a cone-shaped uterus with narrowed fundus and the appendages emerging at the fundus and lower uterine segment on the right and left respectively. This is a rare fusion defect and makes a case for review of the existing uterine malformation classification systems, to make it all encompassing.

Ezeike|Azuka Chinweokwu|AC|
Liman|Idris Mohammed|IM|
Babandi|Rukayya Muhammad|RM|
Austin-Amadi|Elizabeth Obebhatein|EO|
Dantata|Hafsa Aminu|HA|
Ubani|Felix Ugo|FU|

incidental
uterine
fusion
abnormality
Case Report


Quasi-projective synchronization of fractional-order complex-valued recurrent neural networks.

Abstract: In this paper, without separating the complex-valued neural networks into two real-valued systems, the quasi-projective synchronization of fractional-order complex-valued neural networks is investigated. First, two new fractional-order inequalities are established by using the theory of complex functions, Laplace transform and Mittag-Leffler functions, which generalize traditional inequalities with the first-order derivative in the real domain. Additionally, different from hybrid control schemes given in the previous work concerning the projective synchronization, a simple and linear control strategy is designed in this paper and several criteria are derived to ensure quasi-projective synchronization of the complex-valued neural networks with fractional-order based on the established fractional-order inequalities and the theory of complex functions. Moreover, the error bounds of quasi-projective synchronization are estimated. Especially, some conditions are also presented for the Mittag-Leffler synchronization of the addressed neural networks. Finally, some numerical examples with simulations are provided to show the effectiveness of the derived theoretical results.

Yang|Shuai|S| Yu|Juan|J| Hu|Cheng|C| Jiang|Haijun|H|

Quasi-projective synchronization
Complex-valued neural network
Fractional-order derivative
Linear feedback control