Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats.

Abstract:
OBJECTIVE
To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats.

METHODS
125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined.

RESULTS
Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p<0.05).

CONCLUSIONS
Hemin may be beneficial in protecting against focal cerebral hypoxic-ischemia through inducing the expression of exogenous Ngb.

Song|Xue|X| Xu|Rui|R| Xie|Fei|F| Zhu|Haiyuan|H| Zhu|Ji|J| Wang|Xin|X|

D020244:Infarction, Middle Cerebral Artery

Hemin
neuroprotection
neuroglobin
focal cerebral hypoxic-ischemia


Working Memory Load and Negative Picture Processing: Neural and Behavioral Associations With Panic, Social Anxiety, and Positive Affect.

Abstract:
BACKGROUND
Internalizing disorders such as anxiety may be characterized by an imbalance between bottom-up (stimulus-driven) and top-down (goal-directed) attention. The late positive potential (LPP) can be used to assess these processes when task-irrelevant negative and neutral pictures are presented within a working memory paradigm. Prior work using this paradigm has found that working memory load reduces the picture-elicited LPP across participants; however, anxious individuals showed a reduced effect of working memory load on the LPP, suggesting increased distractibility.

METHODS
The current study assessed transdiagnostic associations between specific symptom dimensions of anxiety, the LPP, and behavior in a clinically representative, heterogeneous group of 76 treatment-seeking patients with internalizing disorders, who performed a working memory task interspersed with negative and neutral pictures.

RESULTS
As expected, negative pictures enhanced the LPP, and working memory load reduced the LPP. Participants with higher social anxiety showed increased LPPs to negative stimuli during early and late portions of picture presentation. Panic symptoms were associated with reduced LPPs to negative pictures compared with neutral pictures as well as a reduced effect of working memory load on the LPP during the late time window. Reduced positive affect was associated with greater behavioral interference from negative pictures.

CONCLUSIONS
Hypervigilance for negative stimuli was uniquely explained by social anxiety symptoms, whereas panic symptoms were associated with the opposing effect-blunted processing/avoidance of these stimuli. Panic symptoms were uniquely associated with reduced top-down control. Results reveal distinct associations between neural reactivity and anxiety symptom dimensions that transcend traditional diagnostic boundaries.

MacNamara|Annmarie|A|
Jackson|T Bryan|TB|
Fitzgerald|Jacklynn M|JM|
Hajcak|Greg|G|
Phan|K Luan|KL|

Panic
Social anxiety
Late positive potential
LPP
Transdiagnostic
ERP


Neonatal Lipopolysaccharide Infection Causes Demyelination and Behavioral Deficits in Adult and Senile Rat Brain.

Abstract:
BACKGROUND
Neonatal bacterial infections have been reported to cause white matter loss, although studies concerning the influence of infection on the expression of myelin and aging are still in their emerging state.

PURPOSE
The present study aimed to investigate the effects of perinatal lipopolysaccharide (LPS) exposure on the myelination at different age points using histochemical and immunocytochemical techniques and the relative motor coordination.

METHODS
A rat bacterial infection model was established by exposing the neonatal rats with LPS (0.3 mg/kg body weight, i.p., on postnatal day (PND) 3 followed by a booster at PND 5) and its impact was studied on the myelination and motor coordination in young, adult, and senile rats.

RESULTS
The results obtained suggest that the administration of LPS induces demyelination, predominantly in cortex and corpus callosum. Low expression level of myelin oligodendrocyte glycoprotein (MOG) was observed at all time points, with prominence at 12, 18, and 24 months of age. In addition, reduced staining with luxol fast blue stain was also recorded in the experimentals. With the increasing demyelination and declining motor ability, LPS exposure also seemed to accelerate normal aging symptoms.

CONCLUSION
There is a direct correlation of myelin damage and poor motor coordination with age. This would provide a better incite to understand inflammation-associated demyelinating changes in age-associated neurodegenerative disorders. Since, no long-term studies on behavioral impairments caused by LPS-induced demyelination in the central nervous system has been reported so far, this work would help in the better understanding of the long-term pathological effects of bacterial-induced demyelination.

Singh|Kavita|K| Patro|Nisha|N| Pradeepa|M|M| Patro|Ishan|I|

Demyelination
Myelin oligodendrocyte glycoprotein
Lipopolysacchride
Motor behavior


Preparation and use of resuscitation equipment to assess and treat children in emergency situations.

Abstract: This article uses the (A) Airway, (B) Breathing and, (C) Circulation structured approach to the assessment of a sick child to provide an overview of the equipment used in resuscitation attempts involving children. It emphasises that a working knowledge of the resuscitation equipment used in emergency situations is fundamental to the process of checking and preparing it. The article is aimed at students and newly qualified nurses, but may be also useful as revision for more experienced nurses.

D000293:Adolescent
D016887:Cardiopulmonary Resuscitation
D002648:Child
D002675:Child, Preschool
D004509:Education, Nursing, Continuing
D004632:Emergency Medical Services
D006323:Heart Arrest
D006801:Humans
D007223:Infant
D007231:Infant, Newborn
D009740:Nursing Staff
D010371:Pediatric Nursing
D017410:Practice Guidelines as Topic

Biological processes
emergency nursing
fluid balance
intubation
paediatric respiration
paediatric resuscitation


Quantitative bone single-photon emission CT/CT parameters reflect pain and functional status of symptomatic basal joint arthritis of the thumb.

Abstract:
AIMS
The aim of this study was to assess arthritis of the basal joint of the thumb quantitatively using bone single-photon emission CT/CT (SPECT/CT) and evaluate its relationship with patients' pain and function.

METHODS
We retrospectively reviewed 30 patients (53 hands) with symptomatic basal joint arthritis of the thumb between April 2019 and March 2020. Visual analogue scale (VAS) scores for pain, grip strength, and pinch power of both hands and Patient-Rated Wrist/Hand Evaluation (PRWHE) scores were recorded for all patients. Basal joint arthritis was classified according to the modified Eaton-Glickel stage using routine radiographs and the CT scans of SPECT/CT, respectively. The maximum standardized uptake value (SUVmax) from SPECT/CT was measured in the four peritrapezial joints and the highest uptake was used for analysis.

RESULTS
According to Eaton-Glickel classification, 11, 17, 17, and eight hands were stage 0 to I, II, III, and IV, respectively. The interobserver reliability for determining the stage of arthritis was moderate for radiographs (k = 0.41) and substantial for CT scans (k = 0.67). In a binary categorical analysis using SUVmax, pain (p < 0.001) and PRWHE scores (p = 0.004) were significantly higher in hands with higher SUVmax. Using multivariate linear regression to estimate the pain VAS, only SUVmax (B 0.172 (95% confidence interval (CI) 0.065 to 0.279; p = 0.002) showed a significant association. Estimating the variation of PRWHE scores using the same model, only SUVmax (B 1.378 (95% CI, 0.082 to 2.674); p = 0.038) showed a significant association.

CONCLUSION
The CT scans of SPECT/CT provided better interobserver reliability than routine radiographs for evaluating the severity of arthritis. A higher SUVmax in SPECT/CT was associated with more pain and functional disabilities of basal joint arthritis of the thumb. This approach could be used to complement radiographs for the evaluation of patients with this condition. Cite this article: Bone Joint J 2021;103-B(8):1380-1385.

D000072098:Single Photon Emission Computed Tomography Computed Tomography


Perturbation of nuclear-cytosolic shuttling of Rx1 compromises extreme resistance and translational arrest of potato virus X transcripts.

Abstract: Many plant intracellular immune receptors mount a hypersensitive response (HR) upon pathogen perception. The concomitant localized cell death is proposed to trap pathogens, such as viruses, inside infected cells, thereby preventing their spread. Notably, extreme resistance (ER) conferred by the potato immune receptor Rx1 to potato virus X (PVX) does not involve the death of infected cells. It is unknown what defines ER and how it differs from HR-based resistance. Interestingly, Rx1 can trigger an HR, but only upon artificial (over)expression of PVX or its avirulence coat protein (CP). Rx1 has a nucleocytoplasmic distribution and both pools are required for HR upon transient expression of a PVX-GFP amplicon. It is unknown whether mislocalized Rx1 variants can induce ER upon natural PVX infection. Here, we generated transgenic Nicotiana benthamiana producing nuclear- or cytosol-restricted Rx1 variants. We found that these variants can still mount an HR. However, nuclear- or cytosol-restricted Rx1 variants can no longer trigger ER or restricts viral infection. Interestingly, unlike the mislocalized Rx1 variants, wild-type Rx1 was found to compromise CP protein accumulation. We show that the lack of CP accumulation does not result from its degradation but is likely to be linked with translational arrest of its mRNA. Together, our findings suggest that translational arrest of viral genes is a major component of ER and, unlike the HR, is required for resistance to PVX.

D002467:Cell Nucleus
D003600:Cytosol
D060467:Disease Resistance
D010935:Plant Diseases
D010940:Plant Proteins
D017863:Potexvirus
D011198:Solanum tuberosum

virus
cell death
Nicotiana benthamiana
NLR
plant immunity
translational inhibition


A novel approach to infertility treatment of advance-age patient with prominent intramural fibroid.

Abstract: We report for the first time on a case of infertile advance-age patient with large intramural fibroid, who conceived following a course of Ulipristal. The patient underwent two fresh fertility preserving IVF cycles, with cryopreservation of 9 day-3 embryos, followed by a 12 weeks course of Ulipristal (5 mg per day) and a subsequent frozen-thawed embryo transfer with her own previously cryopreserved embryos. We, therefore, believe that Ulipristal is a valuable addition to treatment armamentarium of advance-age infertile patient with prominent intramural fibroid.

Orvieto|Raoul|R|
Zilberberg|Eran|E|
Vanni|Valeria Stella|VS|
Botchan|Amnom|A|

Fibroid Ulipristal IVF cryopreservation FET


Contextualizing ovarian pain in the late 19th century - Part 2: Ovarian-based treatments of "hysteria".

Abstract: The peculiar therapeutic practice of "ovarian compression"-paradoxically, both in initiating and in terminating hysterical activity-remains largely unexplained territory from both historical and medical perspectives. The gynecological indications of "hysteria" and "hystero-epilepsy" are now considered to be among similar questionable indications as contemporaneous "nymphomania" and "epilepsy." This article analyzes historical clinical observations, as well as surgical experiences of the time, to determine if there has been a uniform understanding of the ovarian contribution to "hystero-epilepsy." The respective findings are interpreted in light of the physiology of "chronic pelvic pain." Evidence for pain as a source of hystero-epileptic attacks is further represented through a series of clinical photographs suggesting a link to current problems, such as severe left-lower-quadrant pain. The emerging insights link more clearly to the functional role (le rôle fonctionnel) of the ovaries in relation to the "fits" of hystero-epileptic patients, while validating women's pain experiences during the latter part of the nineteenth century. Differences in the interpretation of disease concepts between Robert Battey (1828-1895) and Octave Terrillon (1844-1895) thereby permit an understanding of variations in the use of the removal of women's ovaries for pain.

Hysteria
hystero-epilepsy
ovaries
nineteenth century
neuropsychiatric patient experience
ovarian compression
pain theories


Bile acids LCA and CDCA inhibited porcine deltacoronavirus replication in vitro.

Abstract: Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes gastroenteritis in pigs and no vaccines or antiviral drugs are available. Bile acids are active factors in intestines and influence the replication of enteric viruses. Currently, the role of bile acids on PDCoV replication is unknown. In this study, we tested the effects of different types of bile acids on the replication of PDCoV in cell culture. We found that physiological concentrations of bile acids chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) had antiviral activity against PDCoV in porcine kidney cell line (LLC-PK1) and porcine small intestinal epithelial cell line (IPEC-J2). In IPEC-J2 cells, CDCA and LCA inhibited PDCoV replication at post-entry stages by inducing the production of interferon (IFN)-λ3 and IFN-stimulated gene 15 (ISG15) via G protein-coupled receptor (GPCR). In summary, bile acids CDCA and LCA restricted PDCoV infection and LCA functioned through a GPCR-IFN-λ3-ISG15 signaling axis in IPEC-J2 cells. Our results may open new avenues for the development of antiviral drugs to treat PDCoV infection in pigs.

Kong|Fanzhi|F| Niu|Xiaoyu|X| Liu|Mingde|M| Wang|Qiuhong|Q|

D000818:Animals
D001647:Bile Acids and Salts
D002635:Chenodeoxycholic Acid
D000085686:Deltacoronavirus
D004847:Epithelial Cells
D054884:Host-Pathogen Interactions
D007372:Interferons
D018374:LLC-PK1 Cells
D008095:Lithocholic Acid
D013552:Swine
D013553:Swine Diseases
D014779:Virus Replication

Bile acids
Porcine deltacoronavirus
Interferon


A Basal Forebrain Site Coordinates the Modulation of Endocrine and Behavioral Stress Responses via Divergent Neural Pathways.

Abstract:
UNLABELLED
The bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH). Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure. Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress. Follow-up experiments probed axonal pathways emanating from the anteroventral BST which accounted for separable endocrine and behavioral functions subserved by this cell group. The PVH and ventrolateral periaqueductal gray were recipients of GABAergic outputs from the anteroventral BST that were necessary to restrain stress-induced HPA activation and passive coping behavior, respectively, during TS and forced swim tests. In contrast to other BST subdivisions implicated in anxiety-like responses, these results direct attention to the anteroventral BST as a nodal point in a stress-modulatory network for coordinating neuroendocrine and behavioral coping responses, wherein impairment could account for core features of stress-related mood disorders.

SIGNIFICANCE STATEMENT
Dysregulation of the neural pathways modulating stress-adaptive behaviors is implicated in stress-related psychiatric illness. While aversive situations activate a network of limbic forebrain regions thought to mediate such changes, little is known about how this information is integrated to orchestrate complex stress responses. Here we identify novel roles for the anteroventral bed nuclei of the stria terminalis in inhibiting both stress hormone output and passive coping behavior via divergent projections to regions of the hypothalamus and midbrain. Inhibition of these projections produced features observed with rodent models of depression, namely stress hormone hypersecretion and increased passive coping behavior, suggesting that dysfunction in these networks may contribute to expression of pathological changes in stress-related disorders.

D050496:Vesicular Glutamate Transport Proteins

bed nuclei of the stria terminalis
HPA
paraventricular hypothalamus
behavioral coping
corticosterone
periaqueductal gray area


Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function.

Abstract: The SMCR8-WDR41-C9ORF72 complex is a regulator of autophagy and lysosomal function. Autoimmunity and inflammatory disease have been ascribed to loss-of-function mutations of Smcr8 or C9orf72 in mice. In humans, autoimmunity has been reported to precede amyotrophic lateral sclerosis caused by mutations of C9ORF72 However, the cellular and molecular mechanisms underlying autoimmunity and inflammation caused by C9ORF72 or SMCR8 deficiencies remain unknown. Here, we show that splenomegaly, lymphadenopathy, and activated circulating T cells observed in Smcr8  mice were rescued by triple knockout of the endosomal Toll-like receptors (TLRs) TLR3, TLR7, and TLR9. Myeloid cells from Smcr8  mice produced excessive inflammatory cytokines in response to endocytosed TLR3, TLR7, or TLR9 ligands administered in the growth medium and in response to TLR2 or TLR4 ligands internalized by phagocytosis. These defects likely stem from prolonged TLR signaling caused by accumulation of LysoTracker-positive vesicles and by delayed phagosome maturation, both of which were observed in Smcr8  macrophages. Smcr8  mice also showed elevated susceptibility to dextran sodium sulfate-induced colitis, which was not associated with increased TLR3, TLR7, or TLR9 signaling. Deficiency of WDR41 phenocopied loss of SMCR8. Our findings provide evidence that excessive endosomal TLR signaling resulting from prolonged ligand-receptor contact causes inflammatory disease in SMCR8-deficient mice.

McAlpine|William|W|
Sun|Lei|L|
Wang|Kuan-Wen|KW|
Liu|Aijie|A|
Jain|Ruchi|R|
San Miguel|Miguel|M|
Wang|Jianhui|J|
Zhang|Zhao|Z|
Hayse|Braden|B|
McAlpine|Sarah Grace|SG|
Choi|Jin Huk|JH|
Zhong|Xue|X|
Ludwig|Sara|S|
Russell|Jamie|J|
Zhan|Xiaoming|X|
Choi|Mihwa|M|
Li|Xiaohong|X|
Tang|Miao|M|
Moresco|Eva Marie Y|EMY|
Beutler|Bruce|B|0000-0002-3639-246X
Turer|Emre|E|

D047908:Intracellular Signaling Peptides and Proteins

inflammation
Toll-like receptor
inflammatory bowel disease
vesicle trafficking


Role of methylthioadenosine/S-adenosylhomocysteine nucleosidase in Vibrio cholerae cellular communication and biofilm development.

Abstract: In Vibrio cholerae, the genes required for biofilm development are repressed by quorum sensing at high cell density due to the accumulation in the medium of two signaling molecules, cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2). A significant fraction of toxigenic V. cholerae isolates, however, exhibit dysfunctional quorum sensing pathways. It was reported that transition state analogs of the enzyme methylthioadenosine/S-adenosylhomocysteine nucleosidase (MtnN) required to make AI-2 inhibited biofilm formation in the prototype quorum sensing-deficient strain N16961. This finding prompted us to examine the role of both autoinducers and MtnN in biofilm development and virulence gene expression in a quorum sensing-deficient genetic background. Here we show that deletion of mtnN encoding methylthioadenosine/S-adenosylhomocysteine nucleosidase, cqsA (CAI-1), and/or luxS (AI-2) do not prevent biofilm development. However, two independent mtnN mutants exhibited diminished growth rate and motility in swarm agar plates suggesting that, under certain conditions, MtnN could influence biofilm formation indirectly. Nevertheless, MtnN is not required for the development of a mature biofilm.

Silva|Anisia J|AJ|
Parker|William B|WB|
Allan|Paula W|PW|
Ayala|Julio C|JC|
Benitez|Jorge A|JA|

D001426:Bacterial Proteins
D018441:Biofilms
D013437:Carbon-Sulfur Lyases
D002465:Cell Movement
D007659:Ketones
D009699:N-Glycosyl Hydrolases
D011683:Purine-Nucleoside Phosphorylase
D053038:Quorum Sensing
D014734:Vibrio cholerae

S-adenosylhomocysteine nucleosidase
Vibrio cholerae
Biofilm
Quorum sensing
Methylthioadenosine nucleosidase


Comparison of Central and Peripheral Bone Mineral Density Measurements in Postmenopausal Women.

Abstract:
Objectives
The purpose of the current study was to compare central and peripheral bone mineral density at different regions including spine, hip, and wrist in postmenopausal women.

Methods
Forty postmenopausal women participated in this study. Their mean age, body mass, height, and body mass index were 53.5 ± 2.75 y, 68.6 ± 8.68 kg, 167.8 ± 6.46 cm, and 24.31 ± 1.69 kg/m2, respectively. Bone mineral density (BMD) T-scores of spine, hip, and wrist regions were measured for all participants with a dual-energy X-ray absorptiometry scan.

Results
All measured regions (spine, hip, and wrist) had low BMD T-scores. Bone mineral density of the wrist was significantly lower (-2.58 ± 2.18) than that of both spine (-1.79 ± 0.98) and hip (-1.69 ± 1.37). In addition, there were no statistically significant differences in BMD between the spine and hip.

Conclusions
In this group of postmenopausal women, wrist BMD decreased more than spine and hip BMD. Both spine and hip BMD decreased by nearly the same percentage in postmenopausal women. Peripheral sites may be more representative of osteoporosis than central sites. Trial Registration: PACTR201602001478123.

Postmenopause
Spine
Hip
Wrist
Bone Density
Osteoporosis, Postmenopausal


Robust polyimide nano/microfibre aerogels welded by solvent-vapour for environmental applications.

Abstract: Due to the high porosity, resilience and ultra-low density, polymer nanofibre-derived aerogels (NFAs) have been widely investigated in recent years. However, welding of the fibrous networks of NFAs, which has been proved extremely essential to their structural performance, still remains a major challenge. Herein, electrospun polyimide (PI) nano/microfibres were used as building blocks to construct hierarchically porous aerogels through a solid-templating technique. By further welding the adjacent nano/microfibres at their cross-points in a controllable fashion by solvent-vapour, super elasticity was achieved for the aerogels, with a recoverable ultimate strain of 80%. It is noteworthy that this process is free from cross-linking, heating and significant structure changing (i.e. chemical structure, crystallinity and fibrous network). Additionally, the porous structure of PI nano/microfibre aerogels (PI-N/MFAs) could be tuned by adjusting the organization of microfibres from a disordered/ordered cellular to a uniform structure. The as-obtained aerogels showed ultra-low density (4.81 mg cm-3), high porosity (99.66%), and comparable or higher recoverable compressive strain and stress relative to the other nanofibre-based aerogels. Furthermore, we showed the potential of such an aerogel for particle or aerosol filtration. PI nanofibre aerogels composite filters (PI-NFACFs) manifested excellent performance in PM2.0 filtration (99.6% filtration efficiency with 115 Pa pressure drop). Therefore, this study brought a new perspective on the simple preparation of nanofibre-based aerogels for air filtration.

Shen|Ying|Y|0000-0002-2472-1844 Li|Dawei|D| Deng|Bingyao|B|0000-0001-5652-3503 Liu|Qingsheng|Q| Liu|Huizhong|H| Wu|Tong|T|

nano/microfibre aerogels
air filtration
electrospinning
solvent-vapour treatment


Identification of novel chicken CD4⁺ CD3⁻ blood population with NK cell like features.

Abstract: Chicken NK cells have been defined in embryonic spleen and intestinal epithelium as CD8(+) lymphoid cells that lack BCR and TCR, whereas blood NK cells have not been phenotypically defined. Here we employed the mab, 8D12 directed against CHIR-AB1, a chicken Fc receptor, to define a previously uncharacterized lymphoid cell population in the blood. Although CHIR-AB1 expression was found on several cell populations, cells with extraordinary high CHIR-AB1 levels ranged between 0.4 and 2.8% in five different chicken lines. The widespread applicability of the CHIR-AB1 mab was unexpected, since CHIR-AB1-like genes form a polygenic and polymorphic subfamily. Surprisingly the CHIR-AB1 high cells coexpressed low MHCII, low CD4 and CD5, while other T cell markers CD3 and CD8, the B cell marker Bu1, the macrophage marker KUL01 were absent. Moreover, they stained with the mab 28-4, 20E5 and 1G7, which define chicken NK cells and they also expressed CD25, CD57, CD244 and the vitronectin receptor (αVβ3 integrin). In functional assays, PMA stimulation led to high levels of IFNγ release, while spontaneous cytotoxicity was not detectable. The expression of typical NK cell markers in the absence of characteristic B- or T-cell markers, and their IFNγ release is suggestive of a yet unidentified NK like population.

Neulen|Marie-Luise|ML|
Viertlboeck|Birgit C|BC|
Straub|Christian|C|
Göbel|Thomas W|TW|

D053645:Interleukin-2 Receptor alpha Subunit

D000071176:Signaling Lymphocytic Activation Molecule Family

Chicken
Fc receptors
CD4
Natural killer cells


Ten-year experience of pulsed intravenous cyclophosphamide and methylprednisolone protocol (PICM protocol) in severe ocular inflammatory disease.

Abstract:
AIMS
Severe ocular inflammation is a blinding ophthalmological emergency. This study evaluates the efficacy and patient tolerance of a validated regime of pulsed intravenous cyclophosphamide and methylprednisolone ('PICM protocol') for these patients.

METHODS
26 patients with severe inflammatory eye disease (43 eyes: 22 uveitis, 21 scleritis/sclerokeratitis; median age 52 years (IQR 40.25-62.25)) presenting to a regional tertiary referral centre were recruited over a 10-year period (January 2002-December 2011) into the PICM protocol, comprising intravenous cyclophosphamide 15 mg/kg, intravenous methylprednisolone 10 mg/kg, maximum nine pulses over 20 weeks supplemented with low-dose continuous oral prednisolone. Data were captured pretreatment and at 6 and 12 months follow-up. Primary outcome measures were control of inflammation according to standard criteria and reduction in systemic glucocorticoid to ≤10 mg prednisolone/day.

RESULTS
A median of six pulses (IQR 5-6) were administered over a median of 3 months (IQR 2.25-4). In the scleritis/sclerokeratitis group, 15/21(71%) achieved success or partial success at 6 and 12 months versus 9/22 (41%) for the same time points in the uveitis group (χ(2)=4.058, p=0.044). Two patients had adverse events requiring treatment withdrawal.

CONCLUSIONS
This PICM protocol is a well-tolerated regimen for managing severe ocular inflammation and appears particularly useful in patients with scleritis/sclerokeratitis.

Khan|Imran J|IJ|
Barry|Robert J|RJ|
Amissah-Arthur|Kwesi N|KN|
Carruthers|David|D|
Elamanchi|Srinivasa Rao|SR|
Situnayake|Deva|D|
Murray|Philip I|PI|
Denniston|Alastair K|AK|
Rauz|Saaeha|S|

Inflammation
Cornea
Retina
Sclera and Episclera
Treatment Medical


Dietary phytate has a greater anti-nutrient effect on feed conversion ratio compared to body weight gain and greater doses of phytase are required to alleviate this effect as evidenced by prediction equations on growth performance, bone ash and phytate degradation in broilers.

Abstract: Cobb 400, male broilers (n=4,752) were fed one of 12 diets, with 12 pens/diet and 33 birds/pen. Treatments consisted of 3 levels of phytate P (0.24, 0.345, or 0.45%) and 4 doses of phytase (0, 500, 1,000, or 2,000 phytase units (FTU)/kg). Diets were formulated with reduced Ca (0.22%), available P (0.20%), energy (80 to 120 kcal/kg), and amino acids (1 to 5%) when compared with breed requirements. Prediction equations suggested feeding dietary phytate P > 0.275, 0.295, or 0.319% reduced feed intake (FI) and body weight gain (BWG) and increased feed conversion ratio, respectively, from day 0 to 21. Supplementing phytase at 561, 1,285, or >2,000 FTU/kg resulted in the maximum FI, BWG, or feed efficiency, respectively. From day 0 to 42, maximum BWG or feed efficiency were achieved at phytate P concentrations <0.281 or 0.25%, respectively. Supplementing phytase at 449 or 2,000 FTU/kg maximized BWG or feed efficiency, respectively. Tibia ash weight, percent or Ca concentration were maximized at phytate P concentrations <0.24, 0.296, or 0.24%, respectively and phytase supplementation at 822 or >2,000 FTU/kg maximized tibia ash weight or percent respectively. In the absence of phytase, phytate (IP6) concentration in the gizzard was greatest in birds fed 0.45% phytate P and phytase supplementation between 1,132 to 1,285 FTU/kg resulted in the lowest IP6 concentration in the gizzard. There was no effect of dietary phytate P on the concentration of phytate esters (IP5 or IP4) in the gizzard, which were minimized at 1,208 FTU/kg of phytase. In the absence of phytase, the concentration of phytate ester (IP3) or inositol in the gizzard was greatest in birds fed 0.345% phytate P and phytase supplementation at ∼500 FTU/kg minimized IP3, whereas 2,000 FTU/kg maximized inositol, except in birds fed 0.45% phytate P, which was maximized at 202 FTU/kg of phytase. Prediction equations can be useful to determine the influence of phytase and phytate P on broiler performance, phytate degradation and bone ash.

D000824:Animal Nutritional Physiological Phenomena


Biocompatible fluorescent carbon dots derived from roast duck for in vitro cellular and in vivo C. elegans bio-imaging.

Abstract: Biocompatible fluorescent carbon dots (CDs) were prepared via a simple and green route using duck breasts as a natural carbon source. The CDs from duck breasts were well dispersed, and their mean particle size decreased from 2.59 to 1.95 nm when the roasting temperature increased from 200 to 300 °C. Abundant functional groups such as OH, COOH, and NH2 were observed on the surface of the CDs, providing the CDs with good water solubility. These CDs emitted strong fluorescence under ultraviolet light irradiation and exhibited superior photostability. The absolute fluorescence quantum yield of CDs rose from 10.53% to 38.05% when the relative nitrogen content of CDs increased from 7.18% to 12.73%. The CDs showed low toxicity to PC12 cells for prolonged exposure. Therefore, the duck CDs were successfully developed as fluorescent probes for in vitro PC12 cells and in vivo Caenorhabditis elegans imaging. These results indicated that the CDs derived from roast duck were biocompatible and can potentially be used as probes in bio-imaging.

Cong|Shuang|S| Liu|Kangjing|K| Qiao|Fengzhi|F| Song|Yukun|Y| Tan|Mingqian|M|

Carbon dots
Roast duck
Bio-imaging
Fluorescent probes
Formation


Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents.

Abstract:
BACKGROUND
IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN.

METHODS
Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape.

RESULT
"GSE25590" (miRNA) and "GSE73953" (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with "Innate immune system", "Apoptosis", as well as "NGF signaling" pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN.

CONCLUSION
Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers.

Gholaminejad|Alieh|A| Gheisari|Yousof|Y| Jalali|Sedigheh|S| Roointan|Amir|A|

IgA nephropathy
Biomarkers
Gene expression
Computational biology
Gene regulatory network


Nanotechnology in medicine and relevance to dermatology: present concepts.

Abstract: Nanotechnology and nanomedicine are complementary disciplines aimed at the betterment of human life. Nanotechnology is an emerging branch of science for designing tools and devices of size 1-100 nm, with unique functions at the cellular, atomic and molecular levels. The concept of using nanotechnology in medical research and clinical practice is known as nanomedicine. Today, nanotechnology and nanoscience approaches to particle design and formulations are beginning to expand the market for many drugs and forming the basis for a highly profitable niche within the industry, but some predicted benefits are hyped. Under many conditions, dermal penetration of nanoparticles may be limited for consumer products such as sunscreens, although additional studies are needed on potential photooxidation products, experimental methods and the effect of skin condition on penetration. Today, zinc oxide and titanium dioxide nanoparticles (20-30 nm) are widely used in several topical skin care products such as sunscreens. Thus, in the present scenario, nanotechnology is spreading its wings to address the key problems in the field of medicine. The benefits of nanoparticles have been shown in several scientific fields, but very little is known about their potential to penetrate the skin. Hence, this review discusses in detail the applications of nanotechnology in medicine with more emphasis on the dermatologic aspects.

nanotechnology
Nanomedicine
nanoparticles
silver
skin absorption


Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination.

Abstract: The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the detailed mechanism is not understood. We report cryo-EM structures of human Dot1L bound to (1) H2BK120Ub and (2) unmodified nucleosome substrates at 3.5 Å and 4.9 Å, respectively. Comparison of both structures, complemented with biochemical experiments, provides critical insights into the mechanism of Dot1L stimulation by H2BK120Ub. Both structures show Dot1L binding to the same extended surface of the histone octamer. In yeast, this surface is used by silencing proteins involved in heterochromatin formation, explaining the mechanism of their competition with Dot1. These results provide a strong foundation for understanding conserved crosstalk between histone modifications found at actively transcribed genes and offer a general model of how ubiquitin might regulate the activity of chromatin enzymes.

Valencia-Sánchez|Marco Igor|MI|
De Ioannes|Pablo|P|
Wang|Miao|M|
Vasilyev|Nikita|N|
Chen|Ruoyu|R|
Nudler|Evgeny|E|
Armache|Jean-Paul|JP|
Armache|Karim-Jean|KJ|

structure
ubiquitin
cryo-EM
nucleosome
Dot1
histone modifications
chromatin
H3K79
histone cross-talk
methylation


Identification of lanthionine and lysinoalanine in heat-treated wheat gliadin and bovine serum albumin using tandem mass spectrometry with higher-energy collisional dissociation.

Abstract: The present manuscript reports on the identification of various dehydroamino acid-derived bonds and cross-links resulting from thermal treatment (excess water, 240 min, 130 °C) of two model food proteins, bovine serum albumin, and wheat gliadin. S-Carbamidomethylated tryptic and chymotryptic digests of unheated (control) and heated serum albumin and gliadin, respectively, were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI-MS/MS) with higher-energy collisional dissociation (HCD). Heat-induced β-elimination of cystine, serine and threonine, and subsequent Michael addition of cysteine and lysine to dehydroalanine and 3-methyl-dehydroalanine were demonstrated. Lanthionine, lysinoalanine, 3-methyl-lanthionine, and 3-methyl-lysinoalanine were identified. The detection of inter-chain lanthionine in both bovine serum albumin and wheat gliadin suggests the significance of these cross-links for food texture.

Rombouts|Ine|I|
Lambrecht|Marlies A|MA|
Carpentier|Sebastien C|SC|
Delcour|Jan A|JA|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Higher-energy collisional dissociation
β-Elimination
Michael addition
LC–ESI–MS/MS
Orbitrap
Protein cross-links


Minute lesions of alveolar damage in lungs of patients with stable idiopathic pulmonary fibrosis.

Abstract:
AIMS
To investigate the mechanisms underlying the acute exacerbation of idiopathic pulmonary fibrosis, and in particular the role of minute lesions of alveolar damage.

METHODS AND RESULTS
We examined surgical lung biopsy samples from 38 patients with stable idiopathic pulmonary fibrosis, and evaluated the association between the foci and development of acute exacerbation. Mild extravasation, probably resulting from lung injury and intra-alveolar oedema fluid, were observed in narrow areas of architecturally intact lung tissue. Minute lesions of alveolar damage were detected in these areas. Alveolar epithelial cells in these lesions were injured. Hypoxia-inducible factor-2α-positive macrophages, tumour necrosis factor-α-positive macrophages and neutrophils had accumulated in alveolar spaces in and around these lesions. Cases were classified into patients without (17) and with (21) minute lesions of alveolar damage. Development to acute exacerbation (five cases) occurred only in patients with minute lesions of alveolar damage (P = 0.03).

CONCLUSIONS
The formation of minute lesions of alveolar damage may be initiated by hypoxia, and such lesions play important roles in the development of acute exacerbation.

Emura|Iwao|I| Usuda|Hiroyuki|H| Togashi|Kenichi|K| Satou|Kazuhiro|K|

D051792:Basic Helix-Loop-Helix Transcription Factors

minute lesion of alveolar damage
idiopathic pulmonary fibrosis
acute exacerbation
macrophage
neutrophil
hypoxia-inducible factor-2α
tumour necrosis factor-α


Beyond RAS and BRAF: a target rich disease that is ripe for picking.

Abstract: Despite numerous breakthroughs in the understanding of colorectal cancer and identification of many oncogenic mutations, the treatment of metastatic colorectal cancer remains relatively more empiric than targeted. Testing for mutations in rat sarcoma virus (RAS) and rapidly growing fibrosarcoma (RAF) are routinely performed, though identification of these mutations currently offers little more than a negative predictive marker for response to EGFR inhibitor treatment and, in the case of RAF mutation, a poor prognostic indicator. Next-generation sequencing has identified both common and rare mutations in colorectal cancer that offer options for more advanced, targeted therapy. With so much research invested in these targets, the treatment of metastatic colorectal cancer stands to become much more personalized in the near future. This review describes several of the more promising targets that are currently being investigated in advanced colorectal cancer.

Friedrich|Tyler|T|
Leong|Stephen|S|
Lieu|Christopher H|CH|

mitogen-activated protein kinases (MAPKs)


Polycyclic aromatic hydrocarbons in teas using QuEChERS and HPLC-FLD.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) are food-processing contaminants considered to be carcinogenic and genotoxic. Due to its drying process stage, teas may be contaminated with PAHs. The aim of the study was to validate an analytical method involving QuEChERS and HPLC-FLD for the determination of PAH4 in teas and evaluate the contamination levels in 10 different types of teas from Brazil. Recoveries varied from 54% to 99% and relative standard deviations from 1% to 21%. Limits of detection and quantification were from 0.03 to 0.3 µg/kg and 0.1 to 0.5 µg/kg, respectively. Mate tea presented the highest PAH levels, with PAH4 varying from 194 to 1795 µg/kg; followed by black (1.8-186 µg/kg), white (24-119 µg/kg), and green teas (3.1-92 µg/kg). Teas with lowest PAH4 were strawberry, lemongrass, peppermint, and boldo. Only trace levels of PAHs were detected in tea infusions, so apparently it would not affect PAH intake by Brazilian population.

Tfouni|Silvia A V|SAV|
Reis|Raquel M|RM|
Kamikata|Kamille|K|
Gomes|Fernanda M L|FML|
Morgano|Marcelo A|MA|
Furlani|Regina P Z|RPZ|

D053000:Analytic Sample Preparation Methods

D002851:Chromatography, High Pressure Liquid

Polycyclic aromatic hydrocarbons
tea
QuEChERS
mate
Camellia sinensis


ANALYSIS OF HISTORICAL MEDICAL RECORDS OF CALIFORNIA CONDORS ( GYMNOGYPS CALIFORNIANUS) ADMITTED FOR LEAD EXPOSURE TO THE LOS ANGELES ZOO AND BOTANICAL GARDENS BETWEEN 1997 AND 2012: A CASE SERIES STUDY.

Abstract: Lead toxicosis remains the primary cause of death in wild populations of California condors ( Gymnogyps californianus). Many condors require medical intervention with lead chelation therapy, among other conservation measures, to survive in the wild. An analysis of historical medical records of California condors admitted for lead exposure to the Los Angeles Zoo and Botanical Gardens (LA Zoo) between 1997 and 2012 was performed to investigate clinical presentation, radiographic findings, and treatment along with the potential impact of these factors on recovery and successful release back into the wild. Of 100 individual condors presented to the LA Zoo for suspected lead toxicosis during this period, 84 condors had records for initial laboratory blood lead levels. For these 84 condors (40 [47.6%] females and 44 [52.4%] males), 277 initial laboratory blood lead levels in total were recorded because of repeated admissions. Thirty-two (38%) condors were admitted once to the zoo and 62% were admitted two or more times. Clinical signs were not observed in 87.5% of the condors admitted with median blood lead concentrations of 26 μg/dl. Of the radiographs taken on initial presentation, 65% did not show evidence of gastrointestinal metallic foreign bodies. Various treatments protocols with edetatum calcium disodium, dimercaptosuccinic acid, and lactated Ringer's solution were documented in the medical records. Of the 277 admissions, 154 admissions had a recorded outcome posttreatment of which 140 (91%) admissions were released back to the wild. This study contributes to a better understanding of how intervention and therapeutic approaches have been essential for the recovery, release, and sustainability of these birds as a wild population. Consistency in data collection of California condors admitted for diagnosis and treatment of lead toxicosis is needed to better assess the impacts of medical interventions.

Nguyen|Natalie|N|
Saggese|Miguel D|MD|
Eng|Curtis|C|

D003247:Conservation of Natural Resources

California condor
lead toxicosis
chelation
radiographs
clinical signs


Is Aging in Place Delaying Nursing Home Admission?

Abstract:
OBJECTIVES
This study examines whether aging in place (community-based living before admission to a nursing home) delays nursing home admission among New York State home health care recipients.

DESIGN
Retrospective cohort study (January 2007-December 2012).

SETTING
New York State.

PARTICIPANTS
Adults age 65+ who received home health services for at least 2 months before permanent nursing home admission.

MEASUREMENT AND ANALYSIS
Permanent transition is defined as home care patients who are discharged to and stay at a nursing home for more than 3 months. Data were abstracted from the Minimum Data Set (MDS) and Outcome and Assessment Information Set (OASIS). Descriptive and bivariate Kruskal-Wallis and χ(2) tests were performed.

RESULTS
The average age of nursing home residents at admission remained steady at 83 years between 2007 and 2012. The proportion of minority populations (Asian, black, Hispanic/Latino) increased, whereas the white population declined (P < .0001). The average length of stay at home increased 8 months, from 17 months in 2007 to 25 months in 2012 (P < .0001). Chronic conditions with significant increases in prevalence during the study period were hypertension (P < .0009), dementia (P < .0001), heart failure (P = .05), urinary incontinence (P < .0001), and bowel incontinence (P < .0001). Increases in functional disabilities requiring extensive human assistance included toileting, dressing, personal hygiene, and transferring (all P < .001).

CONCLUSION
Home health services enabled recipients to remain at home 8 months longer, thus delaying nursing home entry. Given the increase in prevalence of comorbidities and disability, we anticipate a concomitant increase in support services at the nursing home. These results may inform policy and staffing decisions regarding adjustments in required caregivers' credentials and nurse-patient ratios.

Young|Yuchi|Y| Kalamaras|John|J| Kelly|Lindsay|L| Hornick|David|D| Yucel|Recai|R|

D000203:Activities of Daily Living
D000368:Aged
D000369:Aged, 80 and over
D002908:Chronic Disease
D015331:Cohort Studies
D005260:Female
D006699:Home Care Services
D006801:Humans
D057187:Independent Living
D008297:Male
D009518:New York
D009735:Nursing Homes
D010343:Patient Admission
D012189:Retrospective Studies
D013997:Time Factors

Aging in place
nursing home
ADLs
home and community-based services


Removal of arsenic from water using manganese (III) oxide: Adsorption of As(III) and As(V).

Abstract: Removal of arsenic from water was evaluated with manganese (III) oxide (Mn2O3) as adsorbent. Adsorption of As(III) and As(V) onto Mn2O3 was favorable according to the Langmuir and Freundlich adsorption equilibrium equations, while chemisorption of arsenic occurred according to the Dubinin-Radushkevich equation. Adsorption parameters from the Langmuir, Freundlich, and Temkin equations showed a greater adsorption and removal of As(III) than As(V) by Mn2O3. Maximum removal of As(III) and As(V) occurred at pH 3-9 and at pH 2, respectively, while removal of As(V) in the pH range of 6-9 was 93% (pH 6) to 61% (pH 9) of the maximum removal. Zeta potential measurements for Mn2O3 in As(III) was likely converted to As(V) solutions indicated that As(III) was likely converted to As(V) on the Mn2O3 surface at pH 3-9. Overall, the effective Mn2O3 sorbent rapidly removed As(III) and As(V) from water in the pH range of 6-9 for natural waters.

D052918:Environmental Restoration and Remediation

arsenic
Adsorption
As(III)
As(V)
pH
manganese oxides


Impact of titanium dioxide on androgen receptors, seminal vesicles and thyroid hormones of male rats: possible protective trial with aged garlic extract.

Abstract: The aim of this study was to evaluate the effect of titanium dioxide (TiO2 ), a widely produced and consumed pigment in various food products, on the post-natal development of male albino rat seminal vesicle and thyroid hormones, as well as to evaluate the ameliorative effect of aged garlic extract (AGE) on TiO2 -induced alterations. Forty male rat pups (3 weeks old) were divided into four equal groups. The 1st group received distilled water orally (control group), 2nd group was given 2 ml kg-1 AGE, 3rd group was administered TiO2 (5 g kg-1 BW) day after day for 65 days, and the 4th group administered AGE 6 hr prior to TiO2 gavage. TiO2 -exposed rats showed nonsignificant changes in the serum testosterone, TSH, T3 and T4 , while serum glucose showed a significant decrease. Androgen receptor (AR) mRNA expression was significantly down-regulated and weak signal of AR immune labelling. Histopathologically, the epithelium cell lining of seminal vesicles showed focal areas of necrosis and fibrous tissue with the prominent fibrous stroma of the atrophied glands. Meanwhile, AGE supplementation ameliorated the deleterious effects of TiO2 intoxication through protecting the tissues from oxidative stress caused by TiO2 . In summary, oral administration of TiO2 resulted in abnormal developmental events in male rat seminal vesicle and AGE able to reduce TiO2 toxicity.

Abu Zeid|E H|EH|
Alam|R T M|RTM|
Abd El-Hameed|N E|NE|

titanium dioxide
Androgen receptors
seminal vesicles
thyroid hormones
immune histochemistry
quantitative real-time PCR


Medial thalamic stroke and its impact on familiarity and recollection.

Abstract: Models of recognition memory have postulated that the mammillo-thalamic tract (MTT)/anterior thalamic nucleus (AN) complex would be critical for recollection while the Mediodorsal nucleus (MD) of the thalamus would support familiarity and indirectly also be involved in recollection (Aggleton et al., 2011). 12 patients with left thalamic stroke underwent a neuropsychological assessment, three verbal recognition memory tasks assessing familiarity and recollection each using different procedures and a high-resolution structural MRI. Patients showed poor recollection on all three tasks. In contrast, familiarity was spared in each task. No patient had significant AN lesions. Critically, a subset of 5 patients had lesions of the MD without lesions of the MTT. They also showed impaired recollection but preserved familiarity. Recollection is therefore impaired following MD damage, but familiarity is not. This suggests that models of familiarity, which assign a critical role to the MD, should be reappraised.

familiarity
recollection
recognition memory
thalamus
MRI
amnesia
human
neuroscience


Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure.

Abstract: Flash nanoprecipitation (FNP) is a widely used technique to prepare particulate carriers based on various polymers, and it was proven to be a promising technology for the industrial production of drug loaded nanoparticles. However, up to now, only its application to hydrophobic compounds has been deeply studied and the encapsulation of some strongly hydrophilic compounds, such as caffeine, remains a challenge. Caffeine loaded poly-ε-caprolactone (PCL) nanoparticles were produced in a confined impinging jet mixer using acetone as the solvent and water as the antisolvent. Caffeine was dissolved either in acetone or in water to assess the effects of two different process conditions. Nanoparticles properties were assessed in terms of loading capacity (LC%), encapsulation efficiency (EE%), and in vitro release kinetics. Samples were further characterized by dynamic light scattering, scanning electron microscopy, X-ray photo electron spectroscopy, and infrared spectroscopy to determine the size, morphology, and structure of nanoparticles. FNP was proved an effective technique for entrapping caffeine in PCL and to control its release behavior. The solvent used to solubilize caffeine influences the final structure of the obtained particles. It was observed that the active principle was preferentially adsorbed at the surface when using acetone, while with water, it was embedded in the matrix structure. The present research highlights the possibility of extending the range of applications of FNP to hydrophilic molecules.

flash nanoprecipitation
nanoparticles
hydrophilic compound
caffeine
PCL
encapsulation efficiency
CIJM
drug delivery
solvent displacement
surface properties


Tuberculosis infection via the emergency department among inpatients in South Korea: a propensity score matched analysis of the National Inpatient Sample.

Abstract:
BACKGROUND
Emergency departments (EDs) carry a high risk of infectious disease transmission and have also been implicated in tuberculosis (TB) outbreaks.

AIM
To determine if patients who visit EDs have an increased risk of TB infection. Using South Korean inpatient sample data (2012), the risk of TB occurrence during 90 days after hospitalization for patients admitted via EDs was compared with that for patients admitted via outpatient clinics.

METHODS
The data of the 2012 Health Insurance Review and Assessment Service - National Inpatient Sample were used. TB diagnosis was based on International Classification of Diseases Version 10 [all TB (A15-A19), pulmonary TB (A15-A16) and extrapulmonary TB (A17-A18)].

FINDINGS
After propensity score matching using the demographic and clinical characteristics of the patients, 191,997 patients (64,017 patients admitted via EDs and 127,908 patients admitted via outpatient clinics) were included in this study. There was no significant difference in baseline patient characteristics between the two groups. The percentage of patients with TB admitted via EDs was higher than that of patients admitted via outpatient clinics. The likelihood of active TB occurrence was 30% higher for all TB [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.12-1.52] and pulmonary TB (HR 1.30; 95% CI 1.10-1.53) in patients admitted via EDs compared with patients admitted via outpatient clinics; this difference was significant. However, no difference in the occurrence of extrapulmonary TB was observed between the two groups.

CONCLUSIONS
The likelihood of TB infection was greater in patients admitted via EDs than in patients admitted via outpatient clinics.

Min|J-Y|JY| Kim|H-J|HJ| Yoon|C|C| Lee|K|K| Yeo|M|M| Min|K-B|KB|

Inpatient
Propensity score matching
TB
Nosocomial infections


Establishing the Biofidelity of a Multiphysics Finite Element Model of the Human Heart.

Abstract:
PURPOSE
Accelerating development of new therapeutic cardiac devices remains a clinical and technical priority. High-performance computing and the emergence of functional and complex in silico models of human anatomy can be an engine to accelerate the commercialization of innovative, safe, and effective devices.

METHODS
An existing three-dimensional, nonlinear model of a human heart with flow boundary conditions was evaluated. Its muscular tissues were exercised using electrophysiological boundary conditions, creating a dynamic, electro-mechanical simulation of the kinetics of the human heart. Anatomic metrics were selected to characterize the functional biofidelity of the model based on their significance to the design of cardiac devices. The model output was queried through the cardiac cycle and compared to in vivo literature values.

RESULTS
For the kinematics of mitral and aortic valves and curvature of coronary vessels, the model's performance was at or above the 95th percentile range of the in vivo data from large patient cohorts. One exception was the kinematics of the tricuspid valve. The model's mechanical use environment would subject devices to generally conservative use conditions.

CONCLUSIONS
This conservative simulated use environment for heart-based medical devices, and its judicious application in the evaluation of medical devices is justified, but careful interpretation of the results is encouraged.

D001021:Aortic Valve
D001696:Biomechanical Phenomena
D003198:Computer Simulation
D020342:Finite Element Analysis
D006801:Humans
D008955:Models, Cardiovascular

Biofidelity
Finite element
Computational
Medical devices
Anthromorphometric
Living Heart


Mental Health of Flying Cabin Crews: Depression, Anxiety, and Stress Before and During the COVID-19 Pandemic.

Abstract: Objectives: Initially, we analyzed relations between the challenging working conditions of flight attendants with symptoms of depression, anxiety and stress. As the COVID-19 pandemic plunged airlines into an unprecedented crisis, its impact on the mental health of flying cabin crews became the focus of a second survey. Methods: Flight attendants were surveyed online with DASS-21 in May 2019 (N = 105; sample 1) and April 2020 (N = 1119; sample 2), complemented with questions about working conditions (in 2019) and existential fears and fear of job loss (in 2020). Results: Sample 1 revealed that symptoms of depression, anxiety and stress highly correlated with the subjective assessment of working conditions, but not with objectifiable parameters. Sample 2 showed significant positive correlations between existential fears and fear of job loss with depression, anxiety and stress. Crew members, grounded in April 2020, showed significantly higher scores in depression and stress, while still flying individuals had more clinically relevant symptoms of anxiety. Mean value comparisons between sample 1 and 2 in DASS-21 revealed a significant increase in symptoms at the time of crisis with effect sizes of d = 0.63 for depression, d = 0.26 for anxiety, and d = 0.52 for stress. The incidence of clinically relevant symptoms among the respondents increased from 8 to 23% (depression), from 6 to 14% (anxiety), and from 8 to 24% (stress). Conclusion: The COVID-19 pandemic and associated work restrictions coincide with severe impairment of mental health of flying cabin crews, consistent with a mental health protecting function of labor.

depression
anxiety
stress
COVID-19
working conditions
aerospace
aviation
unemployment


Nivolumab and pembrolizumab as immune-modulating monoclonal antibodies targeting the PD-1 receptor to treat melanoma.

Abstract: Malignant melanoma is an important issue in oncology due to its high incidence, high mortality, and resistance to systemic therapy; however, targeted immunotherapy has noticeably improved the survival rates of melanoma patients. Promising targeted immunotherapies for malignant melanoma include the blockade of immune checkpoints with antibodies targeting cytotoxic T lymphocyte-associated antigen 4 and the programmed cell death protein 1 pathway. The US FDA-approved antibody ipilimumab targets cytotoxic T lymphocyte-associated antigen 4; however, it was limited by toxicity and a low response. Nivolumab and pembrolizumab (formerly lambrolizumab), the two FDA-approved anti-programmed death-1 monoclonal antibodies, show highly durable response rates and long-term safety, validating the importance of the programmed cell death protein 1 pathway blockade for treatment of malignant melanoma.

Faghfuri|Elnaz|E|
Faramarzi|Mohammad Ali|MA|
Nikfar|Shekoufeh|S|
Abdollahi|Mohammad|M|

D061026:Programmed Cell Death 1 Receptor

nivolumab
pembrolizumab
monoclonal antibody
PD-1 receptor
melanoma


Change in non-alcoholic beverage sales following a 10-pence levy on sugar-sweetened beverages within a national chain of restaurants in the UK: interrupted time series analysis of a natural experiment.

Abstract:
BACKGROUND
This study evaluates changes in sales of non-alcoholic beverages in Jamie's Italian, a national chain of commercial restaurants in the UK, following the introduction of a £0.10 per-beverage levy on sugar-sweetened beverages (SSBs) and supporting activity including beverage menu redesign, new products and establishment of a children's health fund from levy proceeds.

METHODS
We used an interrupted time series design to quantify changes in sales of non-alcoholic beverages 12 weeks and 6 months after implementation of the levy, using itemised electronic point of sale data. Main outcomes were number of SSBs and other non-alcoholic beverages sold per customer. Linear regression and multilevel random effects models, adjusting for seasonality and clustering, were used to investigate changes in SSB sales across all restaurants (n=37) and by tertiles of baseline restaurant SSB sales per customer.

RESULTS
Compared with the prelevy period, the number of SSBs sold per customer declined by 11.0% (-17.3% to -4.3%) at 12 weeks and 9.3% (-15.2% to -3.2%) at 6 months. For non-levied beverages, sales per customer of children's fruit juice declined by 34.7% (-55.3% to -4.3%) at 12 weeks and 9.9% (-16.8% to -2.4%) at 6 months. At 6 months, sales per customer of fruit juice increased by 21.8% (14.0% to 30.2%) but sales of diet cola (-7.3%; -11.7% to -2.8%) and bottled waters (-6.5%; -11.0% to -1.7%) declined. Changes in sales were only observed in restaurants in the medium and high tertiles of baseline SSB sales per customer.

CONCLUSIONS
Introduction of a £0.10 levy on SSBs alongside complementary activities is associated with declines in SSB sales per customer in the short and medium term, particularly in restaurants with higher baseline sales of SSBs.

D065186:Interrupted Time Series Analysis

sugar-sweetened beverages
natural experiment
diet
interrupted-time series
sugar tax


Role of adjuvant therapy after radical hysterectomy in intermediate-risk, early-stage cervical cancer.

Abstract:
OBJECTIVE
Adjuvant treatment remains a controversial issue for intermediate-risk cervical cancer. The aim of this study was to compare the prognosis of patients who underwent no adjuvant treatment, pelvic radiotherapy alone, or concurrent chemoradiotherapy after radical hysterectomy for intermediate-risk, early-stage cervical cancer.

METHODS
Patients with stage IB1-IIA2 (FIGO 2009) cervical squamous cell carcinoma treated with radical hysterectomy and pelvic lymph node dissection, with negative lymph nodes, surgical margins, or parametria, who had combined intermediate risk factors as defined in the Gynecologic Oncology Group trial (GOG-92; Sedlis criteria) were included in the study. Recurrence-free survival and disease-specific survival were compared.

RESULTS
Of 861 patients included in the analysis, 85 patients received no adjuvant treatment, 283 patients were treated with radiotherapy, and 493 patients with concurrent chemoradiotherapy. After a median follow-up of 63 months (IQR 45 to 84), adjuvant radiotherapy or concurrent chemoradiotherapy was not associated with a survival benefit compared with no adjuvant treatment. The 5-year recurrence-free survival and corresponding disease-specific survival were 87.1%, 84.2%, 89.6% (p=0.27) and 92.3%, 87.7%, 91.4% (p=0.20) in the no adjuvant treatment, radiotherapy alone, and concurrent chemoradiotherapy groups, respectively. Lymphovascular space invasion was the only independent prognostic factor for both recurrence-free survival and disease-specific survival. Additionally, significant heterogeneity exists in Sedlis criteria: higher risk of relapse (HR=1.88; 95% CI 1.19 to 2.97; p=0.007) and death (HR=2.36; 95% CI 1.41 to 3.95; p=0.001) occurred in patients with lymphovascular space invasion and deep 1/3 stromal invasion compared with no lymphovascular space invasion, middle or deep 1/3 stromal invasion, and tumor diameter ≥4 cm.

CONCLUSIONS
Radical hysterectomy alone without adjuvant treatment may achieve a favorable survival for patients with intermediate-risk cervical cancer as defined by Sedlis criteria. Criteria for adjuvant treatment in patients without high risk factors need to be further evaluated.

Cao|Lijie|L| Wen|Hao|H| Feng|Zheng|Z| Han|Xiaotian|X| Zhu|Jun|J| Wu|Xiaohua|X|


Ultrasound as a Sole Modality for Prenatal Diagnosis of Placenta Accreta Spectrum: Potentialities and Pitfalls.

Abstract: Background  Placenta accreta spectrum (PAS) is a significant cause of maternal and neonatal mortality and morbidity. Its prevalence has been rising considerably, primarily due to the increasing rate of primary and repeat cesarean sections. Accurate prenatal identification of PAS allows optimal management because the timing of delivery, availability of blood products, and recruitment of skilled anesthesia, and surgical team can be arranged in advance. Aims and Objectives  This study aimed to (1) study the ultrasound and color Doppler features of PAS, (2) correlate imaging findings with clinical and per-operative/histopathological findings, and (3) evaluate the accuracy of ultrasound for the diagnosis of PAS in patients with previous cesarean section. Materials and Methods  This prospective study was conducted in radiology department of a tertiary care hospital. After screening 1,200 pregnant patients, 50 patients of placenta previa with period of gestation ≥ 24 weeks and history of at least one prior cesarean section were included in the study. Following imaging features were evaluated: (1) gray scale covering intraplacental lacunae, disruption of uterovesical interface, myometrial thinning, loss of retroplacental clear space, and focal exophytic masses; and (2) color Doppler covering intraplacental lacunar flow, hypervascularity of uterine serosa-bladder wall interface, and perpendicular bridging vessels between placenta and myometrium. Study Design  Present study is a prospective one in a tertiary care hospital. Results  Of the 19 PAS cases, 18 were correctly diagnosed on ultrasonography (USG) and confirmed either by histopathological analysis of hysterectomy specimen or per-operatively due to difficulty in placental removal. PAS was correctly ruled out in 27 of 31 patients. The diagnostic accuracy of USG was 90%. The sensitivity, specificity, positive, and negative predictive values were 94.7, 87.1, 81.8, and 96.4%, respectively. Conclusion  Ultrasound is indispensable for the evaluation of pregnant patients. It is an important tool for diagnosing PAS, thereby making the operating team more cautious and better equipped for difficult surgery and critical postoperative care. It can be relied upon as the sole modality to accurately rule out PAS in negative patients, thereby obviating unnecessary psychological stress among patients due to possible hysterectomy.

Gulati|Anshika|A| Anand|Rama|R| Aggarwal|Kiran|K| Agarwal|Shilpi|S| Tomer|Shaili|S|

cesarean
Doppler
hysterectomy
antepartum hemorrhage
maternal mortality
morbidly adherent placenta
placenta accrete
placenta increta
placenta percreta
placental lacunae


Potential Whole-Cell Biosensors for Detection of Metal Using MerR Family Proteins from Enterobacter sp. YSU and Stenotrophomonas maltophilia OR02.

Abstract: Cell-based biosensors harness a cell's ability to respond to the environment by repurposing its sensing mechanisms. MerR family proteins are activator/repressor switches that regulate the expression of bacterial metal resistance genes and have been used in metal biosensors. Upon metal binding, a conformational change switches gene expression from off to on. The genomes of the multimetal resistant bacterial strains, Stenotrophomonas maltophilia Oak Ridge strain 02 (S. maltophilia 02) and Enterobacter sp. YSU, were recently sequenced. Sequence analysis and gene cloning identified three mercury resistance operons and three MerR switches in these strains. Transposon mutagenesis and sequence analysis identified Enterobacter sp. YSU zinc and copper resistance operons, which appear to be regulated by the protein switches, ZntR and CueR, respectively. Sequence analysis and reverse transcriptase polymerase chain reaction (RT-PCR) showed that a CueR switch appears to activate a S. maltophilia 02 copper transport gene in the presence of CuSO4 and HAuCl4·3H2O. In previous studies, genetic engineering replaced metal resistance genes with the reporter genes for β-galactosidase, luciferase or the green fluorescence protein (GFP). These produce a color change of a reagent, produce light, or fluoresce in the presence of ultraviolet (UV) light, respectively. Coupling these discovered operons with reporter genes has the potential to create whole-cell biosensors for HgCl2, ZnCl2, CuSO4 and HAuCl4·3H2O.

Baya|Georgina|G| Muhindi|Stephen|S| Ngendahimana|Valentine|V| Caguiat|Jonathan|J|0000-0003-3089-7608


Pulsed-field gel electrophoresis (PFGE): A review of the "gold standard" for bacteria typing and current alternatives.

Abstract: Pulsed-field gel electrophoresis (PFGE) is considered the "gold standard" for bacteria typing. The method involves enzyme restriction of bacteria DNA, separation of the restricted DNA bands using a pulsed-field electrophoresis chamber, followed by clonal assignment of bacteria based on PFGE banding patterns. Various PFGE protocols have been developed for typing different bacteria, leading it to be one of the most widely used methods for phylogenetic studies, food safety surveillance, infection control and outbreak investigations. On the other hand, as PFGE is lengthy and labourious, several PCR-based typing methods can be used as alternatives for research purposes. Recently, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and whole genome sequencing (WGS) have also been proposed for bacteria typing. In fact, as WGS provides more information, such as antimicrobial resistance and virulence of the tested bacteria in comparison to PFGE, more and more laboratories are currently transitioning from PFGE to WGS for bacteria typing. Nevertheless, PFGE will remain an affordable and relevant technique for small laboratories and hospitals in years to come.

Neoh|Hui-Min|HM|
Tan|Xin-Ee|XE|
Sapri|Hassriana Fazilla|HF|
Tan|Toh Leong|TL|

Bacteria typing
Pulsed-field gel electrophoresis (PFGE)


Surgery for trapeziometacarpal osteoarthritis.

Abstract: Trapeziometacarpal (TMC) osteoarthritis is a common, disabling condition that mostly affects women. The demand for surgical treatment is growing and the patients are becoming younger, adding to the challenge. Surgery can only be proposed after failure of well-conducted conservative treatment and requires a complete X-ray assessment. In the early stages, conservative surgery measures can be used to stabilize the joint or realign it in cases of dysplasia, but in most cases, patients are seen with more advanced arthritis and joint replacement must be considered. The ideal arthroplasty technique has yet to be defined but nevertheless, the chosen technique must be well-suited to the patient's condition. Although many studies have been published on this topic, they do not help us define the treatment indications. Prospective studies focusing on the patient rather than evaluating a certain surgical technique are needed. Trapeziectomy with or without ligament reconstruction is still considered the gold standard, but the challenges associated with treating its complications limit its indications. Arthrodesis, interposition or arthroplasty are also viable therapeutic options. The patient must be sufficiently informed to be able to contribute to choosing the indication.

Gay|A-M|AM| Cerlier|A|A| Iniesta|A|A| Legré|R|R|

Surgery
Trapeziometacarpal osteoarthritis
Arthroplasty
Indication
Interposition
First CM joint arthritis
Prothèse
Rhizarthrose
Thumb basal joint arthritis


Cytokinins Are Abundant and Widespread Among Insect Species.

Abstract: Cytokinins (CKs) are a class of compounds that have long been thought to be exclusively plant growth regulators. Interestingly, some species of phytopathogenic bacteria and fungi have been shown to, and gall-inducing insects have been hypothesized to, produce CKs and use them to manipulate their host plants. We used high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-MS/MS) to examine concentrations of a wide range of CKs in 17 species of phytophagous insects, including gall- and non-gall-inducing species from all six orders of Insecta that contain species known to induce galls: Thysanoptera, Hemiptera, Lepidoptera, Coleoptera, Diptera, and Hymenoptera. We found CKs in all six orders of insects, and they were not associated exclusively with gall-inducing species. We detected 24 different CK analytes, varying in their chemical structure and biological activity. Isoprenoid precursor nucleotide and riboside forms of trans-zeatin (tZ) and isopentenyladenine (iP) were most abundant and widespread across the surveyed insect species. Notably, the observed concentrations of CKs often markedly exceeded those reported in plants suggesting that insects are synthesizing CKs rather than obtaining them from the host plant via tissue consumption, compound sequestration, and bioaccumulation. These findings support insect-derived CKs as means for gall-inducing insects to manipulate their host plant to facilitate cell proliferation, and for both gall- and non-gall-inducing insects to modify nutrient flux and plant defenses during herbivory. Furthermore, wide distribution of CKs across phytophagous insects, including non-gall-inducing species, suggests that insect-borne CKs could be involved in manipulation of source-sink mechanisms of nutrient allocation to sustain the feeding site and altering plant defensive responses, rather than solely gall induction. Given the absence of any evidence for genes in the de novo CK biosynthesis pathway in insects, we postulate that the tRNA-ipt pathway is responsible for CK production. However, the unusually high concentrations of CKs in insects, and the tendency toward dominance of their CK profiles by tZ and iP suggest that the tRNA-ipt pathway functions differently and substantially more efficiently in insects than in plants.

Andreas|Peter|P|
Kisiala|Anna|A|
Emery|R J Neil|RJN|
De Clerck-Floate|Rosemarie|R|
Tooker|John F|JF|
Price|Peter W|PW|
Miller Iii|Donald G|DG|
Chen|Ming-Shun|MS|
Connor|Edward F|EF|

cytokinins
insects
gall-inducing
phytophagous
non-gall inducing


Post-fire carbon dynamics in the tropical peat swamp forests of Brunei reveal long-term elevated CH4 flux.

Abstract: Tropical peatlands hold about 15%-19% of the global peat carbon (C) pool of which 77% is stored in the peat swamp forests (PSFs) of Southeast Asia. Nonetheless, these PSFs have been drained, exploited for timber and land for agriculture, leading to frequent fires in the region. The physico-chemical characteristics of peat, as well as the hydrology of PSFs are affected after a fire, during which the ecosystem can act as a C source for decades, as C emissions to the atmosphere exceed photosynthesis. In this work, we studied the longer-term impact of fires on C cycling in tropical PSFs, hence we quantified the magnitude and patterns of C loss (CO2 , CH4 and dissolved organic carbon) and soil-water quality characteristics in an intact and a degraded burnt PSF in Brunei Darussalam affected by seven fires over the last 40 years. We used natural tracers such as 14 C to investigate the age and sources of C contributing to ecosystem respiration (Reco ) and CH4 , while we continuously monitored soil temperature and water table (WT) level from June 2017 to January 2019. Our results showed a major difference in the physico-chemical parameters, which in turn affected C dynamics, especially CH4 . Methane effluxes were higher in fire-affected areas (7.8 ± 2.2 mg CH4  m-2  hr-1 ) compared to the intact PSF (4.0 ± 2.0 mg CH4  m-2  hr-1 ) due to prolonged higher WT and more optimal methanogenesis conditions. On the other hand, we did not find significant differences in Reco between burnt (432 ± 83 mg CO2  m-2  hr-1 ) and intact PSF (359 ± 76 mg CO2  m-2  hr-1 ). Radiocarbon analysis showed overall no significant difference between intact and burnt PSF with a modern signature for both CO2 and CH4 fluxes implying a microbial preference for the more labile C fraction in the peat matrix.

CH4
tropical peatlands
fire
CO2
C dynamics
radiocarbon
peat oxidative decomposition


Prevalence of skin tears in the extremities among elderly residents at a nursing home in Denmark.

Abstract:
OBJECTIVE
The aim of the study was to determine the prevalence of skin tears in the extremities and explore factors in relation to skin tears in elderly residents at a Danish nursing home.

METHOD
The study was designed as a point prevalence survey and conducted at a nursing home with 140 residents >65 years of age. The residents were assessed for presence, number and location of skin tears. Data were collected using a data collection sheet developed for this study. The survey team consisted of four expert nurses from a university hospital (two dermatology and two wound care nurses). Data were collected over a period of 10 hours spread over two days.

RESULTS
Of the 128 participating residents six had skin tears, yielding a prevalence of 4.6 %. In total, 10 skin tears were observed in the 6 residents. The frequency of previous skin tears was 19.5 %. This frequency was significantly higher in residents with skin tears than in those without skin tears (83.3 % versus 16.4 %, p<0.001). Analysis of the relation between skin tears or previous skin tears versus without skin tears or previous skin tears showed significant differences related to the presence of ecchymosis (76.9 %versus 14.7 %, p<0.0001). There were no other significant factors observed.

CONCLUSION
The low prevalence found in this study may reflect the focus on prevention of skin tears that the nursing home has maintained over the past year. Nevertheless, the appropriate prevention and management of residents with skin tears is an ongoing challenge for health professionals.

prevalence
skin tears
Denmark
ecchymosis
long-term care
quality of life


The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis.

Abstract: Published studies have investigated the prognostic role of cyclooxygenase-2 (COX-2) expression in patients with esophageal cancer (EC), but the result remains controversial. Thus, this meta-analysis was conducted to comprehensively evaluate the impact of COX-2 expression on the prognostic value in patients with EC. Relevant studies were identified from PubMed, EMBASE, and Web of Science databases. Studies that detected the COX-2 expression by immunohistochemistry and evaluated the relationship between COX-2 expression and overall survival (OS) or clinicopathological parameters were used in our analysis. The summary hazard ratios (HRs) or odds ratios were calculated to assess the risk or hazard association. A total of 25 studies, which included 2,465 patients, were included in our meta-analysis. Our analysis suggested that overexpression of COX-2 was associated with poor OS (HR =1.60, 95% CI =1.32-1.94, P<0.001). Subgroup analyses by race, percentage of high/positive COX-2 expression, histology type, treatment, and sample size all suggested significant association. Moreover, overexpression of COX-2 was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and TNM stage. This meta-analysis suggested that overexpression of COX-2 might serve as a prognostic biomarker for EC. Large well-designed prospective studies are needed to confirm our conclusion.

Hu|Zaoxiu|Z| Yang|Yanlong|Y| Zhao|Yonghe|Y| Huang|Yunchao|Y|

cyclooxygenase-2
esophageal cancer
meta-analysis
prognosis


Superbenzene-Porphyrin Gas-Phase Architectures Derived from Intermolecular Dispersion Interactions.

Abstract: A systematic series of superbenzene-porphyrin conjugates was synthesized and characterized. All conjugates show a high degree of cluster formation that correlates to the amount of tert-butylated hexa-peri-hexabenzocoronenes (tBuHBCs) attached to the porphyrin's periphery. Determined by mass spectrometry and X-ray diffraction, van der Waals (vdW) interactions like London dispersions (LD), stemming from solubilizing tert-butyl groups, were identified to be the major reason for the cluster formation. Cluster sizes comprised of more than twenty molecules with masses up to 70 000 Da were observed, which are rare examples of large architectures based on synthetic functional molecules, assembled by dispersion interactions. Novel strategies towards the design of solution processable functional materials, capable of dynamic transformations based on non-covalent synthesis can be envisioned.

Dispersion Interaction
Cluster
Porphyrin
Mass spectrometry
Hexabenzocoronene


Oxygen supply limits the heat tolerance of avian embryos.

Abstract: Physiologists have primarily focused on two potential explanations for heat stress in animals-the classic model of molecular stability and an alternative model of oxygen limitation. Although the classic model has widespread support, the oxygen-supply model applies to many aquatic animals and some terrestrial ones. In particular, the embryonic stage of terrestrial animals seems most susceptible to oxygen limitation because embryos acquire oxygen from the atmosphere by diffusion rather than ventilation. We report experiments confirming the two conditions of the oxygen-supply model in Japanese quail embryos, Coturnix coturnix. Hypoxia (12% O2) greatly reduced the chance of survival at 47.5°C, and hyperoxia greatly improved the chance of survival at 48.5°C. This finding expands the scope of the oxygen-supply model to a terrestrial, endothermic species, suggesting that oxygen supply generally limits the heat tolerance of embryos.

Vimmerstedt|Jon C|JC|
Padilla Pérez|Dylan J|DJ|
Angilletta|Michael J|MJ|
VandenBrooks|John M|JM|

Coturnix coturnix
hypoxia
survival
hyperoxia
temperature


Trunk, pelvis and lower limb walking biomechanics are similarly altered in those with femoroacetabular impingement syndrome regardless of cam morphology size.

Abstract:
BACKGROUND
Studies of walking in those with femoroacetabular impingement syndrome have found altered pelvis and hip biomechanics. But a whole body, time-contiuous, assessment of biomechanical parameters has not been reported. Additionally, larger cam morphology has been associated with more pain, faster progression to end-stage osteoarthritis and increased cartilage damage but differences in walking biomechanics between large compared to small cam morphologies have not been assessed.

RESEARCH QUESTION
Are trunk, pelvis and lower limb biomechanics different between healthy pain-free controls and individuals with FAI syndrome and are those biomechanics different between those with larger, compared to smaller, cam morphologies?

METHODS
Twenty four pain-free controls were compared against 41 participants with FAI syndrome who were stratified into two groups according to their maximum alpha angle. Participants underwent three-dimensional motion capture during walking. Trunk, pelvis, and lower limb biomechanics were compared between groups using statistical parametric mapping corrected for walking speed and pain.

RESULTS
Compared to pain-free controls, participants with FAI syndrome walked with more trunk anterior tilt (mean difference 7.6°, p < 0.001) as well as less pelvic rise (3°, p < 0.001), hip abduction (-4.6°, p < 0.05) and external rotation (-6.5°, p < 0.05). They also had lower hip flexion (-0.06Nm⋅kg-1, p < 0.05), abduction (-0.07Nm⋅kg-1, p < 0.05) and ankle plantarflexion moments (-0.19Nm⋅kg-1, p < 0.001). These biomechanical differences occurred throughout the gait cycle. There were no differences in walking biomechanics according to cam morphology size.

SIGNIFICANCE
Results do not support the hypothesis that larger cam morphology is associated with larger differences in walking biomechanics but did demonstrate general differences in trunk, pelvis and lower limb biomechanics between those with FAI sydrome and pain-free controls. Altered external biomechanics are likely the result of complex sensory-motor strategy resulting from pain inhibition or impingement avoidance. Future studies should examine internal loading in those with FAI sydnrome.

Savage|Trevor N|TN|
Saxby|David J|DJ|
Pizzolato|Claudio|C|
Diamond|Laura E|LE|
Murphy|Nicholas J|NJ|
Hall|Michelle|M|
Spiers|Libby|L|
Eyles|Jillian|J|
Killen|Bryce A|BA|
Suwarganda|Edin K|EK|
Dickenson|Edward J|EJ|
Griffin|Damian|D|
Fary|Camdon|C|
O'Donnell|John|J|
Molnar|Robert|R|
Randhawa|Sunny|S|
Reichenbach|Stephan|S|
Tran|Phong|P|
Wrigley|Tim V|TV|
Bennell|Kim L|KL|
Hunter|David J|DJ|
Lloyd|David G|DG|

Walking
Biomechanics
Femoroacetabular impingement
Cam morphology
Pain


Modeling Mortality Based on Pollution and Temperature Using a New Birnbaum-Saunders Autoregressive Moving Average Structure with Regressors and Related-Sensors Data.

Abstract: Environmental agencies are interested in relating mortality to pollutants and possible environmental contributors such as temperature. The Gaussianity assumption is often violated when modeling this relationship due to asymmetry and then other regression models should be considered. The class of Birnbaum-Saunders models, especially their regression formulations, has received considerable attention in the statistical literature. These models have been applied successfully in different areas with an emphasis on engineering, environment, and medicine. A common simplification of these models is that statistical dependence is often not considered. In this paper, we propose and derive a time-dependent model based on a reparameterized Birnbaum-Saunders (RBS) asymmetric distribution that allows us to analyze data in terms of a time-varying conditional mean. In particular, it is a dynamic class of autoregressive moving average (ARMA) models with regressors and a conditional RBS distribution (RBSARMAX). By means of a Monte Carlo simulation study, the statistical performance of the new methodology is assessed, showing good results. The asymmetric RBSARMAX structure is applied to the modeling of mortality as a function of pollution and temperature over time with sensor-related data. This modeling provides strong evidence that the new ARMA formulation is a good alternative for dealing with temporal data, particularly related to mortality with regressors of environmental temperature and pollution.

D003198:Computer Simulation
D004787:Environmental Pollution
D009010:Monte Carlo Method
D013696:Temperature

Monte Carlo simulation
ARMA models
Birnbaum–Saunders distribution
R software
data dependent over time
maximum likelihood methods
model selection
residuals
sensing and data extraction


15-Deoxy-Δ12,14 -prostaglandin J2 binds and inactivates STAT3 via covalent modification of cysteine 259 in H-Ras-transformed human breast epithelial cells.

Abstract: Signal transducer and activator of transcription 3 (STAT3) has been considered as a potential target for development of anticancer therapeutics. Here, we report a novel mechanism by which the cyclopentenone prostaglandin, 15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ) functions as an allosteric inhibitor of STAT3. 15d-PGJ2 inhibits phosphorylation, dimerization, nuclear translocation, and transcriptional activity of STAT3 in H-Ras-transformed human mammary epithelial cells (MCF10A-Ras) through the Michael addition reaction at cysteine 259 of STAT3. Comparative studies with 15d-PGJ2 analogues reveal that both C12-C13 and C9-C10 double bonds conjugated to the carbonyl group in the cyclopentenone ring of 15d-PGJ2 are essential for STAT3 binding. Antiproliferative and pro-apoptotic activities of 15d-PGJ2 in MCF10A-Ras cells are attributable to covalent modification of STAT3 on Cys259, and mimic the effects induced by mutation of this amino acid.

D015972:Gene Expression Regulation, Neoplastic

STAT3
cyclopentenone prostaglandin
15-deoxy-∆12,14-prostaglandin J2
breast cancer
thiol modification
α,β-unsaturated carbonyl group


Both species sorting and neutral processes drive assembly of bacterial communities in aquatic microcosms.

Abstract: A focus of ecology is to determine drivers of community assembly. Here, we investigate effects of immigration and species sorting (environmental selection) on structuring aquatic bacterial communities in both colonised and previously uncolonised environments. We used nonsterilised and presterilised water from three chemically distinct ponds to establish microcosms, which were opened for 12, 24, 48, 96 or 167 h and then closed again to allow airborne bacterial immigration and subsequent succession. Community similarity, richness, evenness and the parameters of a neutral model were investigated after 167 h. Immigration appeared to govern the assembly of communities in the presterilised water as there were no significant differences in evenness among microcosm communities containing water from each pond. Statistical estimation of neutral model parameters confirmed these findings, because the estimated immigration rate changed significantly with time of exposure to immigration. Species sorting also occurred because significant differences in community similarity (for presterilised and nonsterilised communities) and evenness (only for nonsterilised communities) were detected among microcosms containing different pond water; the magnitude of these differences was greater for communities in nonsterilised microcosms. Our study provides evidence for both processes being important during the colonisation of aquatic environments and presents a novel way to apply the neutral model.

Lee|Jack E|JE|
Buckley|Hannah L|HL|
Etienne|Rampal S|RS|
Lear|Gavin|G|

species sorting
microcosms
Gini coefficient
neutral theory
niche theory
stochastic immigration


Non-invasive Evaluation of Right Ventricular Function with Real-Time 3-D Echocardiography.

Abstract: The aim of this study was to evaluate the accuracy and feasibility of real-time 3-D echocardiography (3-DE) in assessing right ventricular (RV) systolic function. A latex balloon was inserted into the right ventricle of 20 freshly harvested pig hearts which were then passively driven by a pulsatile pump apparatus. The RV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and RV ejection fraction (RVEF), derived from 3-DE, as well as the RVEF obtained from 2-D echocardiography (2-DE) were quantified at different stroke volumes (30-70 mL) and compared with sonomicrometry data. In all comparisons, 3-D GLS, GCS, GAS, 2-D RVEF and 3-D RVEF exhibited strong correlations with sonomicrometry data (r = 0.89, 0.79, 0.74, 0.80, and 0.93, respectively; all p values < 0.001). Bland-Altman analyses revealed slight overestimations of echo-derived GLS, GCS, 2-DE RVEF and 3-DE RVEF compared with sonomicrometry values (bias = 1.55, 2.72, 3.59 and 2.21, respectively). Furthermore, there is better agreement among GLS, 3-D RVEF and the sonomicrometry values than between GCS and 2-D RVEF. Real-time 3-DE is more feasible and accurate for assessing RV function than 2-DE. GLS is a potential alternative parameter for quantifying RV systolic function.

Chen|Ran|R|
Zhu|Meihua|M|
Amacher|Kacie|K|
Wu|Xia|X|
Sahn|David J|DJ|
Ashraf|Muhammad|M|

Right ventricular function
Real-time 3-D echocardiography
Global strain


Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study.

Abstract:
BACKGROUND
Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD.

METHODS
Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays.

RESULTS
Mean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid β 1-42 (Aβ1-42) for AD and levels of P-T181-tau and Aβ1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and Aβ1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau, and Aβ1-42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD.

CONCLUSIONS
Levels of P-S396-tau, P-T181-tau, and Aβ1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.

Fiandaca|Massimo S|MS|
Kapogiannis|Dimitrios|D|
Mapstone|Mark|M|
Boxer|Adam|A|
Eitan|Erez|E|
Schwartz|Janice B|JB|
Abner|Erin L|EL|
Petersen|Ronald C|RC|
Federoff|Howard J|HJ|
Miller|Bruce L|BL|
Goetzl|Edward J|EJ|

Biomarkers
Aβ1–42
Neural exosomes
P-Tau
Preclinical AD


The quantitative structure-activity relationships between GABAA receptor and ligands based on binding interface characteristic.

Abstract:
BACKGROUND
Quantitative Structure Activity Relationship (QSAR) methods based on machine learning play a vital role in predicting biological effect.

OBJECTIVE
Considering the characteristics of the binding interface between ligands and the inhibitory neurotransmitter Gamma Aminobutyric Acid A(GABAA) receptor, we built a QSAR model of ligands that bind to the human GABAA receptor.

METHOD
After feature selection with Mean Decrease Impurity, we selected 53 from 1,286 docked ligand molecular descriptors. Three QSAR models are built using gradient boosting regression tree algorithm based on the different combinations of docked ligand molecular descriptors and ligand-receptor interaction characteristics.

RESULTS
The features of the optimal QSAR model contain both the docked ligand molecular descriptors and ligand-receptor interaction characteristics. The Leave-One-Out-Cross-Validation (Q2 LOO) of the optimal QSAR model is 0.8974, the Coefficient of Determination (R2) for the testing set is 0.9261, the Mean Square Error (MSE) is 0.1862. We also used this model to predict the pIC50 of two new ligands, the differences between the predicted and experimental pIC50 are -0.02 and 0.03 respectively.

CONCLUSION
We found the BELm2, BELe2, MATS1m, X5v, Mor08v, and Mor29m are crucial features, which can help to build the QSAR model more accurately.


Distribution of single-nucleotide variants on protein-protein interaction sites and its relationship with minor allele frequency.

Abstract: Recent advances in DNA sequencing techniques have identified rare single-nucleotide variants with less than 1% minor allele frequency. Despite the growing interest and physiological importance of rare variants in genome sciences, less attention has been paid to the allele frequency of variants in protein sciences. To elucidate the characteristics of genetic variants on protein interaction sites, from the viewpoints of the allele frequency and the structural position of variants, we mapped about 20,000 human SNVs onto protein complexes. We found that variants are less abundant in protein interfaces, and specifically the core regions of interfaces. The tendency to "avoid" the interfacial core is stronger among common variants than rare variants. As amino acid substitutions, the trend of mutating amino acids among rare variants is consistent in different interfacial regions, reflecting the fact that rare variants result from random mutations in DNA sequences, whereas amino acid changes of common variants vary between the interfacial core and rim regions, possibly due to functional constraints on proteins. This study illustrated how the allele frequency of variants relates to the protein structural regions and the functional sites in general and will lead to deeper understanding of the potential deleteriousness of rare variants at the structural level. Exceptional cases of the observed trends will shed light on the limitations of structural approaches to evaluate the functional impacts of variants.

D054730:Protein Interaction Domains and Motifs

rare variants
protein complex
3D structure
nonsynonymous mutations
protein-protein interface


The key contribution of platelet and vascular arachidonic acid metabolism to the pathophysiology of atherothrombosis.

Abstract: Arachidonic acid is one of the most abundant and ubiquitous ω-6 polyunsaturated fatty acid, present in esterified form in the membrane phospholipids of all mammalian cells and released from phospholipids by several phospholipases in response to various activating or inhibitory stimuli. Arachidonic acid is the precursor of a large number of enzymatically and non-enzymatically derived, biologically active autacoids, including prostaglandins (PGs), thromboxane (TX) A2, leukotrienes, and epoxyeicosatetraenoic acids (collectively called eicosanoids), endocannabinoids and isoprostanes, respectively. Eicosanoids are local modulators of the physiological functions and pathophysiological roles of blood vessels and platelets. For example, the importance of cyclooxygenase (COX)-1-derived TXA2 from activated platelets in contributing to primary haemostasis and atherothrombosis is demonstrated in animal and human models by the bleeding complications and cardioprotective effects associated with low-dose aspirin, a selective inhibitor of platelet COX-1. The relevance of vascular COX-2-derived prostacyclin (PGI2) in endothelial thromboresistance and atheroprotection is clearly shown by animal and human models and by the adverse cardiovascular effects exerted by COX-2 inhibitors in humans. A vast array of arachidonic acid-transforming enzymes, downstream synthases and isomerases, transmembrane receptors, and specificity in their tissue expression make arachidonic acid metabolism a fine-tuning system of vascular health and disease. Its pharmacological regulation is central in human cardiovascular diseases, as demonstrated by biochemical measurements and intervention trials.

Platelets
Arachidonic acid
Eicosanoids
Haemostasis
Aspirin
Non-steroidal anti-inflammatory drugs
Thrombosis