Role of anoctamin 5, a gene associated with gnathodiaphyseal dysplasia, in osteoblast and osteoclast differentiation.

Abstract: Anoctamin 5 (Ano5) mutations are responsible for gnathodiaphyseal dysplasia, a rare skeletal syndrome. Despite the close linkage of Ano5 to bone remodeling, the molecular mechanisms underlying the role of Ano5 in bone remodeling remain unknown. In this study, we investigated whether Ano5 regulates osteoblast or osteoclast differentiation to maintain normal bone remodeling. Downregulation of Ano5 expression did not affect osteoblast differentiation and mineralization, while ectopic expression of Ano5 significantly enhanced receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation. Furthermore, Ano5-mediated Akt phosphorylation resulted in nuclear factor of activated T-cells c1 (NFATc1) activation, indicating that Ano5 regulates osteoclast differentiation through activation of the Akt-NFATc1 signaling pathway. Thus, our results suggest a possibility that Ano5 is involved in bone remodeling through regulating the function of osteoclasts rather than that of osteoblasts.

Kim|Jung Ha|JH|
Kim|Kabsun|K|
Kim|Inyoung|I|
Seong|Semun|S|
Kim|Sang Wan|SW|
Kim|Nacksung|N|

D020022:Genetic Predisposition to Disease

Anoctamin 5
Gnathodiaphyseal dysplasia
Osteoblast
Osteoclast


Mouse model of glycogen storage disease type III.

Abstract: Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of the glycogen debranching enzyme (GDE), which is encoded by the Agl gene. GDE deficiency leads to the pathogenic accumulation of phosphorylase limit dextrin (PLD), an abnormal glycogen, in the liver, heart, and skeletal muscle. To further investigate the pathological mechanisms behind this disease and develop novel therapies to treat this disease, we generated a GDE-deficient mouse model by removing exons after exon 5 in the Agl gene. GDE reduction was confirmed by western blot and enzymatic activity assay. Histology revealed massive glycogen accumulation in the liver, muscle, and heart of the homozygous affected mice. Interestingly, we did not find any differences in the general appearance, growth rate, and life span between the wild-type, heterozygous, and homozygous affected mice with ad libitum feeding, except reduced motor activity after 50 weeks of age, and muscle weakness in both the forelimb and hind legs of homozygous affected mice by using the grip strength test at 62 weeks of age. However, repeated fasting resulted in decreased survival of the knockout mice. Hepatomegaly and progressive liver fibrosis were also found in the homozygous affected mice. Blood chemistry revealed that alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities were significantly higher in the homozygous affected mice than in both wild-type and heterozygous mice and the activity of these enzymes further increased with fasting. Creatine phosphokinase (CPK) activity was normal in young and adult homozygous affected mice. However, the activity was significantly elevated after fasting. Hypoglycemia appeared only at a young age (3 weeks) and hyperlipidemia was not observed in our model. In conclusion, with the exception of normal lipidemia, these mice recapitulate human GSD IIIa; moreover, we found that repeated fasting was detrimental to these mice. This mouse model will be useful for future investigation regarding the pathophysiology and treatment strategy of human GSD III.

D006004:Glycogen Debranching Enzyme System

D006010:Glycogen Storage Disease Type III

Mouse model
Glycogen storage disease type III
Glycogen debranching enzyme
GDE
GSD III


Genetic counselor use of self-involving responses in a clinical setting: A qualitative investigation.

Abstract: Self-involving responses are direct expressions of genetic counselors' here-and-now feelings about/reactions to patients. Strategic, sparing use of self-involving responses may enhance practitioner genuineness, likeability, and trustworthiness, decrease patient anxiety, and increase patient trust and engagement. Conversely, they may threaten patients who are uncomfortable with emotional expression or confuse them about the counselor's intentions. Despite theorized benefits and risks, no study has explored genetic counselor self-involving responses. This study explored whether clinical genetic counselors use self-involving responses with their patients, reasons for doing so, and their perceptions of when and why the responses work well versus poorly. Two-hundred sixty-eight genetic counselors, invited via a National Society of Genetic Counselors e-blast, completed an online screening survey. Eighty-nine percent reported using self-involving responses with patients, and 17 were purposively selected to participate in semi-structured phone interviews. Thematic analysis yielded themes regarding potential benefits, risks, counselor factors and context, and patient factors related to using self-involving responses. Benefits include conveying counselor conditions for facilitating counseling process (e.g., genuineness, building rapport, focusing the session, and encouraging the patient to open-up), and counseling outcomes by validating decision-making. Risks of use include hindering counseling processes and outcomes by misperceiving patient feelings, boundary crossing, and being unduly directive. Factors, both from the counselor and the context of the session, include comfort with the technique, mastery of clinical skills, minimal knowledge of patient emotions, type of counseling session, and counselor practice specialty. Patient factors include prior rapport with the counselor, and patient emotionality and cultural background. Findings underscore the need for training about this technique. Future research could examine patients' perceptions of self-involving statements and differences in self-involvement across practice specialties and counseling modalities.

self-involving
qualitative
here-and-now
counseling skills
counseling technique
counselor immediacy
genetic counseling
psychosocial counseling
self-reference


Accuracy of iodine density thresholds for the separation of vertebral bone metastases from healthy-appearing trabecular bone in spectral detector computed tomography.

Abstract:
PURPOSE
To evaluate quantitative iodine density mapping (IDM) with spectral detector computed tomography (SDCT) as a quantitative biomarker for separation of vertebral trabecular bone metastases (BM) from healthy-appearing trabecular bone (HTB).

MATERIALS AND METHODS
IRB-approved retrospective single-center-study of portal venous SDCT datasets acquired between June 2016 and March 2017. Inclusion of 43 consecutive cancer patients with BM and 40 without. Target lesions and non-affected control vertebrae were defined using follow-up imaging, MRI, and/or bone scintigraphy. ID and standard deviation were determined with ROI measures by two readers in (a) bone metastases, (b) HTB of BM patients and controls, and (c) ID of various vessels. Volumetric bone mineral density (vBMD) of the lumbar spine and age were recorded. Multivariate ROC analyses und Wilcoxon test were used to determine thresholds for separation of BM and HTB. p < 0.05 was considered significant.

RESULTS
ID measurements of 40 target lesions and 83 reference measurements of HTB were acquired. Age (p < 0.0001) and vBMD (p < 0.05) affected ID measurements independently in multivariate models. There were significant differences of ID between metastases (n = 43) and HTB ID (n = 124; mean 5.5 ± 0.9 vs. 3.5 ± 0.9; p < 0.0001), however, with considerable overlap. In univariate analysis, increased ID discriminated bone lesions (AUC 0.90) with a maximum combined specificity/sensitivity of 77.5%/90.7% when applying a threshold of 4.5 mg/ml. Multivariate regression models improved significantly when considering vBMD, the noise of ID, and vertebral venous ID (AUC 0.98).

CONCLUSION
IDM of SDCT yielded a statistical separation of vertebral bone lesions and HTB. Adjustment for confounders such as age and lumbar vBMD as well as for vertebral venous ID and lesion heterogeneity improved discrimination of trabecular lesions.

KEY POINTS
• SDCT iodine density mapping provides the possibility for quantitative analysis of iodine uptake in tissue, which allows to differentiate bone lesions from healthy bone marrow. • Age and vBMD have a significant impact on iodine density measurements. • Iodine density measured in SDCT yielded highest sensitivity and specificity for the statistical differentiation of vertebral trabecular metastases and healthy trabecular bone using an iodine density threshold of 4.5 mg/ml (most performant)-5.0 mg/ml (optimized for specificity).

D011857:Radiographic Image Interpretation, Computer-Assisted

Iodine
Bone
Tomography
Diagnosis
Neoplasm metastasis


Combination effects of salts and cold storage on the formation of protein-bound Nɛ-(carboxymethyl)lysine and Nɛ-(carboxyethyl)lysine in raw and subsequently commercially sterilized ground pork.

Abstract: The effects of cold storage (0 °C, 0-8 days) and salts (NaCl, 0.5-5%; NaNO2, 50-150 mg/kg) on the formation of protein-bound Nɛ-(carboxymethyl)lysine (CML) and Nɛ-(carboxyethyl)lysine (CEL) in raw and subsequently commercially sterilized (121 °C, 10 min) pork were investigated. Based upon two-factor analysis of variance (α = 0.05), there was no significant interaction effect between salts and storage time on the levels of CML and CEL in raw or sterile pork; salts and storage time did not significantly affect the amounts of CML and CEL in raw pork. However, in sterile pork, 1.5-5% NaCl treatments led to an average of 7.5-52.6% increase in CML, while NaNO2 resulted in 25.4-37.1% and 21.4-23.4% reduction in CML and CEL, respectively; raw pork stored for 8 days led to 82.5% increase of CML and 32.6% increase of CEL in the sterile products (n = 30), as compared to those without cold storage.

Niu|Lihong|L|
Sun|Xiaohua|X|
Tang|Juming|J|
Wang|Jianhui|J|
Wang|Jing|J|
Rasco|Barbara A|BA|
Lai|Keqiang|K|
Fan|Yuxia|Y|
Huang|Yiqun|Y|

D002851:Chromatography, High Pressure Liquid

D017127:Glycation End Products, Advanced

Storage
Pork
Advanced glycation end-products
Sodium chloride
Sodium nitrite


Social influence on metacognitive evaluations: The power of nonverbal cues.

Abstract: Metacognitive evaluations refer to the processes by which people assess their own cognitive operations with respect to their current goal. Little is known about whether this process is susceptible to social influence. Here we investigate whether nonverbal social signals spontaneously influence metacognitive evaluations. Participants performed a two-alternative forced-choice task, which was followed by a face randomly gazing towards or away from the response chosen by the participant. Participants then provided a metacognitive evaluation of their response by rating their confidence in their answer. In Experiment 1, the participants were told that the gaze direction was irrelevant to the task purpose and were advised to ignore it. The results revealed an effect of implicit social information on confidence ratings even though the gaze direction was random and therefore unreliable for task purposes. In addition, nonsocial cues (car) did not elicit this effect. In Experiment 2, the participants were led to believe that cue direction (face or car) reflected a previous participant's response to the same question-that is, the social information provided by the cue was made explicit, yet still objectively unreliable for the task. The results showed a similar social influence on confidence ratings, observed with both cues (car and face) but with an increased magnitude relative to Experiment 1. We additionally showed in Experiment 2 that social information impaired metacognitive accuracy. Together our results strongly suggest an involuntary susceptibility of metacognitive evaluations to nonverbal social information, even when it is implicit (Experiment 1) and unreliable (Experiments 1 and 2).

Eskenazi|Terry|T| Montalan|Benoît|B| Jacquot|Amélie|A| Proust|Joëlle|J| Grèzes|Julie|J| Conty|Laurence|L|

Social influence
Metacognition
Gaze direction
Decision confidence
Fluency


Mother-Daughter Sexual Communication: Differences by Maternal Sexual Victimization History.

Abstract: Women who experience childhood sexual victimization (CSV) report more problems with sexuality and with parenting during adulthood. Consequently, mothers with a CSV history may have particular difficulty with parent-child sexual communication. We examine this possibility in 184 diverse, low-income mother-adolescent daughter dyads. Mothers and daughters reported on the frequency, tone, and comfort of their sexual communication. Using dyadic approaches to analyses, we tested whether mothers' and daughters' reports, and their level of agreement, differ by maternal CSV history. In dyads with maternal CSV, daughters reported more frequent communication in which they felt less embarrassed, and they perceived their mothers as less embarrassed. Mothers with a CSV history were also more accurate in judging how their daughters feel during sexual communication. Although CSV is associated with many negative outcomes, our results suggest mothers with CSV may approach mother-daughter sexual communication in ways that could reduce sexual risk in offspring.

sexual communication
childhood sexual victimization
childhood sexual abuse


Successful cardiopulmonary resuscitation following minimally invasive pectus excavatum repair: A case report.

Abstract:
INTRODUCTION
Pectus excavatum is the most common congenital chest wall deformity. The minimally invasive repair of pectus excavatum (MIRPE) is the most commonly practiced method of surgical treatment and there is concern that the pectus bar will prevent effective CPR. There are no recorded cases of successful cardiopulmonary resuscitation with pectus bars in place.

PRESENTATION OF CASE
A 17-year-old male with pectus excavatum underwent MIRPE. Two years later, he experienced out-of-hospital cardiac arrest and underwent successful cardiopulmonary resuscitation (CPR) in the field with a pectus bar in place.

DISCUSSION
Successful CPR is possible after MIRPE. Clear identification of patients who have undergone MIRPE and education of CPR providers in providing effective chest compressions and defibrillation for this patient population is necessary.

CONCLUSION
This is the first documented case of successful CPR in a patient with a pectus bar in place who experienced out-of-hospital cardiac arrest.

Glithero|Kyle J|KJ|
Tackett|John J|JJ|
DeMason|Kenneth|K|
Burnweit|Cathy A|CA|

Minimally invasive pectus excavatum repair


Mortality burdens in California due to air pollution attributable to local and nonlocal emissions.

Abstract: Limited research has been conducted on the contributions of local and nonlocal emission sources to ambient fine particulate matter (PM2.5) and ozone (O3) and their associated mortality. In this study, we estimated the total mortality resulting from long-term PM2.5 and O3 exposures in California in 2012 using multiple concentration response functions (CRFs) and attributed the estimated mortality to different emission groups. The point estimates of PM2.5-associated mortality in California ranged from 12,700 to 26,700, of which 53% were attributable to in-state anthropogenic emissions. Based on new epidemiological evidence, we estimated that O3 could be associated with up to 13,700 deaths from diseases of both the respiratory and cardiovascular systems in California. In addition, 75% of the ambient O3 in California was due to distant emissions outside the western United States, leading to 92% of the O3-associated mortality. Overall, distant emissions lead to greater mortality burdens of air pollution in California than local anthropogenic emissions.

Wang|Tianyang|T| Zhao|Bin|B| Liou|Kuo-Nan|KN| Gu|Yu|Y| Jiang|Zhe|Z| Song|Kathleen|K| Su|Hui|H| Jerrett|Michael|M| Zhu|Yifang|Y|

Mortality
Emissions
Fine particulate matter
Ozone


Virtual reality for the assessment of frontotemporal dementia, a feasibility study.

Abstract:
PURPOSE
Behavioral variant frontotemporal dementia (bvFTD) is a non-Alzheimer dementia characterized by difficulty in documenting social-emotional changes. Few investigations have used virtual reality (VR) for documentation and rehabilitation of non-Alzheimer dementias.

METHODS
Five bvFTD patients underwent insight interviews while immersed in a virtual environment. They were interviewed by avatars, their answers were recorded, and their heart rates were monitored. They were asked to give ratings of their stress immediately at the beginning and at the end of the session.

RESULTS
The patients tolerated the head-mounted display and VR without nausea or disorientation, heart rate changes, or worsening stress ratings. Their insight responses were comparable to real world interviews. All bvFTD patients showed their presence in the VR environment as they moved their heads to face and respond to each avatar's questions. The bvFTD patients tended to greater verbal elaboration of answers with larger mean length of utterances compared to their real world interviews.

CONCLUSIONS
VR is feasible and well-tolerated in bvFTD. These patients may have VR responses comparable to real world performance and they may display a presence in the virtual environment which could even facilitate assessment. Further research can explore the promise of VR for the evaluation and rehabilitation of dementias beyond Alzheimer's disease. Implications for Rehabilitation Clinicians need effective evaluation and rehabilitation strategies for dementia, a neurological syndrome of epidemic proportions and a leading cause of disability. Memory and cognitive deficits are the major disabilities and targets for rehabilitation in Alzheimer's disease, the most common dementia. In contrast, social and emotional disturbances are the major disabilities and targets for rehabilitation in behavioral variant frontotemporal dementia (bvFTD), an incompletely understood non-Alzheimer dementia. Virtual reality is a technology that holds great promise for the evaluation and rehabilitation of patients with bvFTD and other non-Alzheimer dementias, and preliminary evidence suggests that this technology is feasible in patients with bvFTD.

Mendez|Mario F|MF|
Joshi|Aditi|A|
Jimenez|Elvira|E|

virtual reality
Frontotemporal dementia
insight


Impact of Target Oxygenation on the Chemical Track Evolution of Ion and Electron Radiation.

Abstract: The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( HO 2 • and O 2 • - ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO 2 • and O 2 • - production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO 2 • and O 2 • - in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported. The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( HO 2 • and O 2 • - ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO 2 • and O 2 • - production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO 2 • and O 2 • - in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

oxygen depletion
ROS
chemical track structure
ion beam therapy
oxygen effect
radiation track chemistry
superoxide anion


Sigma 1 receptor activation modifies intracellular calcium exchange in the G93AhSOD1 ALS model.

Abstract: Aberrations in intracellular calcium (Ca2+) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca2+ concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca2+ cycle (ERMCC). The ER supplies Ca2+ to the mitochondria at close contacts between the two organelles, i.e. the mitochondria-associated ER membranes (MAMs). The Sigma 1 receptor (Sig1R) is enriched at MAMs, where it acts as an inter-organelle signaling modulator. However, its impact on intracellular Ca2+ at the cellular level remains to be thoroughly investigated. Here, we used cultured embryonic mice spinal neurons to investigate the influence of Sig1R activation on intracellular Ca2+ homeostasis in the presence of G93AhSOD1 (G93A), an established ALS-causing mutation. Sig1R expression was increased in G93A motor neurons relative to non-transgenic (nontg) controls. Furthermore, we demonstrated significantly reduced bradykinin-sensitive intracellular Ca2+ stores in G93A spinal neurons, which were normalized by the Sig1R agonist SA4503. Moreover, SA4503 accelerated cytosolic Ca2+ clearance following a) AMPAR activation by kainate and b) IP3R-mediated ER Ca2+ release following bradykinin stimulation in both genotypes. PRE-084 (another Sig1R agonist) did not exert any significant effects on cytosolic Ca2+. Both Sig1R expression and functionality were altered by the G93A mutation, indicating the centrality of Sig1R in ALS pathology. Here, we showed that intracellular Ca2+ shuttling can be manipulated by Sig1R activation, thus demonstrating the value of using the pharmacological manipulation of Sig1R to understand Ca2+ homeostasis.

Tadić|Vedrana|V|
Malci|Ayse|A|
Goldhammer|Nadine|N|
Stubendorff|Beatrice|B|
Sengupta|Saikata|S|
Prell|Tino|T|
Keiner|Silke|S|
Liu|Jingyu|J|
Guenther|Madlen|M|
Frahm|Christiane|C|
Witte|Otto W|OW|
Grosskreutz|Julian|J|

D000690:Amyotrophic Lateral Sclerosis
D000818:Animals
D002118:Calcium
D020013:Calcium Signaling
D002478:Cells, Cultured
D004195:Disease Models, Animal
D006801:Humans
D008297:Male
D008810:Mice, Inbred C57BL
D008822:Mice, Transgenic
D009046:Motor Neurons
D010879:Piperazines
D018091:Receptors, AMPA
D017480:Receptors, sigma
D013116:Spinal Cord
D000072105:Superoxide Dismutase-1


Abstract:
INTRODUCTION
The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic.

AIM
To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells.

METHODS
Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 μM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10-15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H2O2) was measured using the Amplex Red assay and intracellular H2O2 using a fluorescent sensor. In addition, ROS superoxide (O2•-) was measured using a O2•- chemiluminescence enhancer. Both H2O2 and O2•- are known to reduce the bioavailability of nitric oxide, which is the most significant chemical mediator of penile erection. Generation of cellular peroxynitrite (ONOO-) was measured using a chemiluminescence assay with the PNCL probe. Subsequently, we measured the activation of acid sphingomyelinase (ASMase) enzyme by radioenzymatic assay using [14C-methylcholine] sphingomyelin as substrate, and the generation of the proapoptotic C16-ceramide was assessed using the diacylglycerol kinase assay. Endothelial cells apoptosis was measured as a readout of these cells' dysfunction.

MAIN OUTCOME MEASURES
Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway.

RESULTS
Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O2•- and as a result there was reduction in the generation of peroxynitrite in these cells. Subsequently, sildenafil protected the endothelial cells from radiation therapy-induced apoptosis.

STRENGTHS AND LIMITATIONS
This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O2•- and peroxynitrite in endothelial cells. Sildenafil reduced ROS generation by inhibiting the ASMase/ceramide pathway. These studies should be followed in an animal model of ED.

CONCLUSIONS
This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721-1733.

Wortel|R C|RC|
Mizrachi|A|A|
Li|H|H|
Markovsky|E|E|
Enyedi|B|B|
Jacobi|J|J|
Brodsky|O|O|
Cao|J|J|
Lippert|A R|AR|
Incrocci|L|L|
Mulhall|J P|JP|
Haimovitz-Friedman|A|A|

D000818:Animals
D017209:Apoptosis
D002417:Cattle
D042783:Endothelial Cells
D007172:Erectile Dysfunction
D006861:Hydrogen Peroxide
D008297:Male
D019255:NADPH Oxidases
D009569:Nitric Oxide
D018384:Oxidative Stress
D010410:Penile Erection
D017382:Reactive Oxygen Species
D000068677:Sildenafil Citrate

Oxidative Stress
Erectile Dysfunction
Radiation
Reactive Oxygen Species
Endothelial Damage


Erlotinib plus concurrent whole-brain radiation therapy for non-small cell lung cancers patients with multiple brain metastases.

Abstract: Sequencing of the epidermal growth factor receptor (EGFR) gene to identify mutations in lung adenocarcinomas is routine in clinical practice. The use of tyrosine kinase inhibitors (TKIs) has transformed the management of patients with brain metastases harboring EGFR mutations, with improved response rates (RR) and survival. We evaluate the role of concurrent TKI therapy and radiotherapy in this group of patients, considering this data in the context of emerging concepts in this advancing field.

Brain metastasis
non-small cell lung cancer (NSCLC)
whole brain radiotherapy (WBRT)


Evaluation of bone mineral density in patients with chronic low back pain.

Abstract:
STUDY DESIGN
This was designed as a retrospective study.

PURPOSE
We investigated the relationship between bone mineral density (BMD) and chronic lower back pain (LBP).

OVERVIEW OF LITERATURE
In spite of a large number of epidemiological surveys on the prevalence of LBP and BMD measurements completed separately in the general population, the relationship between the two has not been well documented.

METHODS
The study included 171 patients with chronic LBP who underwent the BMD study. The control group was selected from our database regarding BMD without LBP.

RESULTS
A total of 678 subjects, aged 18 to 100 years (mean, 49.9±12.9 years) were included in the study, 25% (n=171) of the subjects had LBP. Compared to those patients without LBP, patients exhibiting LBP had statistically significant lower mean weight, hip and spine BMD and T-score. Lower BMD and T-scores were significant regardless of the age group, gender, menopausal status, and obesity classification.

CONCLUSIONS
Chronic LBP has a negative correlation with hip and spine bone mineral density.

Al-Saeed|Osama|O| Mohammed|Ahmed|A| Azizieh|Fawaz|F| Gupta|Renu|R|

Hip
Absorptiometry, Photon
Bone density
Lumbar vertebrae


Systematic Review of Pooling Sputum as an Efficient Method for Xpert MTB/RIF Tuberculosis Testing during the COVID-19 Pandemic.

Abstract: GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

Lima|Shirley Verônica Melo Almeida|SVMA|

severe acute respiratory syndrome coronavirus 2


Recombinant Expression and Phenotypic Screening of a Bioactive Cyclotide Against α-Synuclein-Induced Cytotoxicity in Baker's Yeast.

Abstract: We report for the first time the recombinant expression of fully folded bioactive cyclotides inside live yeast cells by using intracellular protein trans-splicing in combination with a highly efficient split-intein. This approach was successfully used to produce the naturally occurring cyclotide MCoTI-I and the engineered bioactive cyclotide MCoCP4. Cyclotide MCoCP4 was shown to reduce the toxicity of human α-synuclein in live yeast cells. Cyclotide MCoCP4 was selected by phenotypic screening from cells transformed with a mixture of plasmids encoding MCoCP4 and inactive cyclotide MCoTI-I in a ratio of 1:5×10(4). This demonstrates the potential for using yeast to perform phenotypic screening of genetically encoded cyclotide-based libraries in eukaryotic cells.

Jagadish|Krishnappa|K|
Gould|Andrew|A|
Borra|Radhika|R|
Majumder|Subhabrata|S|
Mushtaq|Zahid|Z|
Shekhtman|Alexander|A|
Camarero|Julio A|JA|

aptamers
biological activity
peptides
protein expression
synuclein


Decontamination of biological agents from drinking water infrastructure: a literature review and summary.

Abstract: This report summarizes the current state of knowledge on the persistence of biological agents on drinking water infrastructure (such as pipes) along with information on decontamination should persistence occur. Decontamination options for drinking water infrastructure have been explored for some biological agents, but data gaps remain. Data on bacterial spore persistence on common water infrastructure materials such as iron and cement-mortar lined iron show that spores can be persistent for weeks after contamination. Decontamination data show that common disinfectants such as free chlorine have limited effectiveness. Decontamination results with germinant and alternate disinfectants such as chlorine dioxide are more promising. Persistence and decontamination data were collected on vegetative bacteria, such as coliforms, Legionella and Salmonella. Vegetative bacteria are less persistent than spores and more susceptible to disinfection, but the surfaces and water quality conditions in many studies were only marginally related to drinking water systems. However, results of real-world case studies on accidental contamination of water systems with E. coli and Salmonella contamination show that flushing and chlorination can help return a water system to service. Some viral persistence data were found, but decontamination data were lacking. Future research suggestions focus on expanding the available biological persistence data to other common infrastructure materials. Further exploration of non-traditional drinking water disinfectants is recommended for future studies.

Decontamination
Drinking water
Infrastructure
Spores
Bacteria
Viruses


Computed tomographic measurement of airway remodeling and emphysema in advanced chronic obstructive pulmonary disease. Correlation with pulmonary hypertension.

Abstract:
RATIONALE
Pulmonary hypertension (PH) is an established complication of advanced chronic obstructive pulmonary disease (COPD) associated with increased mortality. The mechanisms coupling PH and bronchial obstruction are unknown; in particular, PH appears to be unrelated to emphysema. We hypothesized that computed tomographic (CT) measurement of airway remodeling instead of emphysema may correlate with PH in COPD.

OBJECTIVES
We aimed to describe the clinical and CT characteristics of patients with COPD with or without PH and to correlate CT measurements of airway remodeling and emphysema with PH.

METHODS
Data were retrieved from 60 COPD patients who underwent both right heart catheterization and computed tomography in a period of stability and had no other disease known to cause PH. CT measurement of airway wall thickness (WT-Pi10) was used to assess airway remodeling and low lung area percentage (LAA%) to quantify emphysema extent.

MEASUREMENTS AND MAIN RESULTS
Thirty-four of the sixty patients with COPD had PH (mean pulmonary arterial pressure [PAPm] ≥ 25 mm Hg). There was no difference between the two groups regarding age, sex, and spirometric results, whereas there was more profound hypoxemia in the PH group. WT-Pi10 was increased in the patients with COPD and PH and correlated with PAPm (ρ = 0.62; P < 0.001). Conversely, there was no difference or correlation between PAPm and LAA% (ρ = 0.12; P = 0.33). In multivariate analysis (R(2) = 0.53), WT-Pi10 was the independent predictor most associated with PAPm elevation, as compared to hypoxia (PaO2) or pulmonary arterial enlargement (diameter ratio between the pulmonary arterial truncus and the ascending aorta).

CONCLUSIONS
This study demonstrates, for the first time to our knowledge, an association between structural alterations of bronchi and PH in COPD. Unlike quantification of emphysema, CT measurement of airway remodeling correlates with PAPm and could be used to estimate the severity of PH in COPD. Airway remodeling burden is not limited to airflow limitation in the assessment of COPD severity and mortality.

Dournes|Gaël|G| Laurent|François|F| Coste|Florence|F| Dromer|Claire|C| Blanchard|Elodie|E| Picard|François|F| Baldacci|Fabien|F| Montaudon|Michel|M| Girodet|Pierre-Olivier|PO| Marthan|Roger|R| Berger|Patrick|P|

D029424:Pulmonary Disease, Chronic Obstructive

remodeling
pulmonary hypertension
COPD
CT


Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

Abstract:
RATIONALE
Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans.

OBJECTIVES
Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity.

METHODS
Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later.

RESULTS
Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity.

CONCLUSIONS
Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

Wagner|Isabella C|IC|
van Buuren|Mariët|M|
Bovy|Leonore|L|
Morris|Richard G|RG|
Fernández|Guillén|G|

Systems consolidation
Dopamine
Norepinephrine
Ritalin
Synaptic tagging and capture
fMRI


The microbiome of the human skin and its variability in psoriasis and atopic dermatitis.

Abstract: The human organism is inhabited by very diverse microorganisms, which constitute the so-called human microbiome and are necessary for the proper functioning of the macroorganism. The correct microbiome ensures homeostasis of the body. A disturbance in its homeostasis leads to dysbiosis. Such deviations may also be related to the development of inflammatory skin diseases, including atopic dermatitis and psoriasis. This review aims to analyse the most current published data on the microbiome of the human skin and examine its role in cutaneous skin diseases, such as atopic dermatitis and psoriasis. This review was compiled by collaborating dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of current literature was done using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis and/or psoriasis. It has not been yet established whether changes in the microbiome are the cause or consequence of disease (atopic dermatitis/psoriasis). However, it was found that in the cases where pathological microflora predominated, an intensification of lesion severity is observed, while with clinical improvement, commensal microflora is restored. Modification of the composition of the microflora may lead to changes in the activation of the immune system and eventually to the development of inflammatory diseases. Adverse effects on the microbiome may include antibiotics, poor diet, stress and adverse environmental conditions. However, more research is needed to identify exact details and mechanisms.

Mazur|Małgorzata|M| Tomczak|Hanna|H| Lodyga|Martha|M| Czajkowski|Rafał|R| Żaba|Ryszard|R| Adamski|Zygmunt|Z|

microbiome
psoriasis
atopic dermatitis
dysbiosis


Mid-Term Effects of Pulmonary Rehabilitation on Cognitive Function in People with Severe Chronic Obstructive Pulmonary Disease.

Abstract:
Purpose
Cognitive dysfunction is a common impairment associated with COPD. However, little is known about 1) its prevalence among those subjects referred for pulmonary rehabilitation (PR), 2) how it may affect the benefit of PR, 3) whether PR improves cognitive function and 4) whether cognitive dysfunction affects the usability of telehealth technology usually used to deliver in-home PR.

Patients and Methods
Fifty-six subjects with stable COPD (54% females, mean age 62 years (SD 9) and median FEV1 0.9 L (IQR 0.7 to 1.1)) participated in this multicenter observational study and performed 24 sessions of PR. The Montreal Cognitive Assessment tool (MoCA) was used to assess the occurrence of mild cognitive dysfunction (using a screening cutoff <26) at baseline, completion of PR and 3 months of follow-up.

Results
Mild cognitive dysfunction was found in 41 subjects (73% [95% CI: 60 to 83%]). The MoCA score significantly improved following PR for those people with baseline mild cognitive dysfunction (p<0.01). There was no significant difference in clinical outcomes between those people with or without mild cognitive dysfunction following PR nor in the proportion of subjects who were autonomous in using the telemonitoring system (83% compared with 71%, p=0.60).

Conclusion
Mild cognitive dysfunction is highly prevalent among those people with COPD referred for PR but does not affect the benefits of PR nor the usability of a telemonitoring system. PR may improve short- and mid-term cognitive function for those people who experience mild cognitive dysfunction at the time they are referred to PR.

Bonnevie|Tristan|T| Medrinal|Clement|C|0000-0003-3186-4891 Combret|Yann|Y| Debeaumont|David|D| Lamia|Bouchra|B| Muir|Jean-François|JF| Cuvelier|Antoine|A|0000-0003-0263-1845 Prieur|Guillaume|G| Gravier|Francis-Edouard|FE|

pulmonary rehabilitation
cognitive dysfunction
COPD
exercise


Predictors for Depression, Sleep Disturbance, and Subjective Pain among Inpatients with Depressive Disorders during the COVID-19 Pandemic: A Cross-Sectional Study.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic can have a negative impact on patients with mood disorders. The aim of this study is to explore the societal influence of COVID-19 and associated impacts on levels of depression, sleep disturbance, and subjective pain among patients with mood disorders. This cross-sectional study recruited inpatients with depression and bipolar disorder. Levels of depression, sleep disturbance, subjective pain, and related demographic variables were collected through self-reported questionnaires. Potential factors associated with levels of depression, sleep disturbance, and subjective pain were identified using univariate linear regression and further entered into a stepwise multivariate linear regression model to identify the independent predictors. A total of 119 participants were included in the analysis, of whom 50.42% had bipolar disorder and 49.58% had unipolar depression. Multivariate analysis showed that a higher level of depression was associated with female subjects, subjects with partners, present history of psychological trauma, and drinking alcohol. Sleep disturbance was associated with subjects with partners and drinking alcohol. A higher level of subjective pain was associated with a higher level of social anxiety and a history of psychological trauma. The current study identified several predictors of psychological burden and subjective pain among inpatients with depression during the COVID-19 pandemic. Further investigations are warranted to extend the application and generalizability of our results.

depression
sleep disturbance
pain
psychiatric inpatient
social impact


Accelerated degradation of pollutants via a close interface connection in heterojunction, and special solid-liquid interactions.

Abstract: The solid-solid or solid-liquid interfaces are vital for the photocatalytic reaction. Herein, AgI nanoparticles (NPs) attached on the (0 1 1) plane of Ag2WO4 nanorods were synthesized by a facile method at room temperature. The co-crystalization of the two components caused their phase transformation and the existence of a strong interface interaction. Meanwhile, the porous batt-like morphology of AgI NPs provided more contact sites for organic pollutants to induce a strong interaction at the solid-liquid interface. The heterojunction nanocatalyst was found to be highly effective for the degradation and mineralization of various pollutants, including the endocrine-disrupting chemical bisphenol A, the antibiotics sulfamethoxazole and ciprofloxacin, and the azo-dye methyl orange under visible light (λ > 420 nm). Its photocatalytic rate was 91, 52, and 39 times higher than that of bulk AgI, standard TiO2-xNx, and the physical mixture of the two components, respectively. Further studies demonstrated that the strong interactions between the two components and the pollutants promoted the electron transfer from organic pollutants to AgI NPs and then from AgI NPs to Ag2WO4 nanorods, resulting in the rapid oxidation of pollutants and the formation of Ag NPs. The newly formed Ag NPs further accelerated the degradation of pollutants due to a SPR effect and an empty levels feeding role to produce h+ on Ag2WO4, which can oxidize surface-adsorbed H2O into OH. This photocatalytic system provided a platform for understanding solid-solid and solid-liquid interface interaction and a novel design idea for water pollutants removal.

Zhang|Lili|L| Wang|Zhiqiang|Z| Hu|Chun|C| Shi|Baoyou|B|

Pollutants
Strong interface interactions
Heterojunction nanocatalyst
Photodegradation


Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate intracellular ROS and triggers apoptosis via mitochondrial pathway.

Abstract: A series of novel quinoxaline derivatives were synthesized and evaluated for their antiproliferative activity in three human cancer cell lines. Compound 12 exhibited the most potent antiproliferative activity with IC50 in the range of 0.19-0.51 μM. The compound inhibited tubulin polymerization and disrupted the microtubule network, leading to G2/M phase arrest. Furthermore, compound 12 induced ROS production and malfunction of mitochondrial membrane potential. Compound 12 led to cancer cells apoptosis in a dose-dependent manner. Western blot analysis showed that compound 12 induced up-regulation of p21 and affected the expression of cell cycle-related proteins. The binding mode was also probed by molecular docking.

Qi|Jianguo|J|0000-0002-8087-1169 Huang|Jing|J| Zhou|Xiaomin|X| Luo|Wen|W| Xie|Jiaxin|J| Niu|Linqiang|L| Yan|Zhijie|Z| Luo|Yang|Y| Men|Yuhui|Y| Chen|Yanan|Y| Zhang|Yahong|Y| Wang|Jianhong|J|

D050759:Cyclin-Dependent Kinase Inhibitor p21

quinoxaline derivatives
tubulin polymerization inhibitors
G2/M phase arrest
cell apoptosis
reactive oxygen species


Spiritual Needs and Perception of Quality of Care and Satisfaction With Care in Hematology/Medical Oncology Patients: A Multicultural Assessment.

Abstract:
CONTEXT
Assessment and response to patients' spiritual concerns are crucial components of high-quality supportive care. Better measures of spiritual needs across the cultural spectrum may help direct necessary interventions.

OBJECTIVES
The objective of this study was to assess spiritual needs in a racially/ethnically and religiously mixed sample of hematology and oncology outpatients and examine the association between spiritual needs and perception of quality of care and satisfaction with care.

METHODS
This is an observational study of 727 racially/ethnically and religiously diverse outpatients. Spiritual needs were measured using a validated, 23-item questionnaire, the Spiritual Needs Assessment for Patients. Scales were administered in four languages.

RESULTS
Forty-four percent were white, 13% Hispanic, 25% black, and 14% Asian. English was the primary language for 57%; 59% considered themselves "spiritual but not religious." At least one spiritual need was reported by 79%. Forty-eight percent were comfortable having their physician inquire about spiritual needs. Compared with English-speaking patients, Russian-speaking patients reported lower spiritual needs (P = 0.003). Patients who considered themselves "spiritual but not religious" (P = 0.006) reported a higher level of spiritual needs. Higher spiritual needs were associated with less satisfaction with care (P = 0.018) and lower perception of quality of care (P = 0.002).

CONCLUSION
Spiritual needs are common in an ethnically, religiously, and linguistically diverse cancer patient population but may differ by cultural background. High levels of spiritual need are associated with lower levels of satisfaction and diminished perception of quality of care. Training clinicians to address patients' spiritual concerns, with attention to cultural differences, may improve patients' experiences of care.

Astrow|Alan B|AB|
Kwok|Gary|G|
Sharma|Rashmi K|RK|
Fromer|Nelli|N|
Sulmasy|Daniel P|DP|

Spirituality
spiritual needs
quality of care
satisfaction with care
spiritual care


Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer.

Abstract: Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

bone marrow adipocyte
adipocytokine
breast cancer
bone metastasis
adipokine


Can local infiltration of lidocaine reduce the postoperative atrial fibrillation rate in patients undergoing lobectomy for lung cancer?

Abstract: Background: Postoperative atrial fibrillation (POAF) occurs frequently after lung cancer surgery. Unfortunately, owing to the multifactorial etiology of POAF, no single drug or intervention can prevent POAF in all cases. The effects of local interventions after lung cancer surgery are unknown. This study investigated the effects of local infiltration of an anesthetic (lidocaine) on the post-lobectomy POAF rate.Methods: This non-randomized study included 81 patients who underwent lobectomy for lung cancer. Patients were divided into a lidocaine-infiltration group comprising patients who received lidocaine infiltration around the pulmonary veins and a no-intervention group. Patients were monitored for the development of POAF during hospitalization. Pre- and postoperative demographic and clinical data were analyzed.Results: AF occurred in 3 (7.5%) of 40 patients in the lidocaine-infiltration group and in 10 (24.39%) of 41 patients in the standard surgical resection group. Overall, it was observed that intraoperative lidocaine infiltration resulted in a lower POAF rate (p < .05).Conclusion: Local infiltration of lidocaine around the pulmonary veins in patients undergoing lobectomy for lung cancer was associated with a lower incidence of POAF, which is attributable to the local anesthetic and autonomic effects of lidocaine.

lidocaine
Atrial fibrillation
lobectomy (lung)
lung cancer-surgery


In vitro comparison in a manikin model: increasing apical enlargement with K3 and K3XF rotary instruments.

Abstract:
INTRODUCTION
The aim of the study was to compare the K3 and K3XF systems (SybronEndo, Glendora, CA) after 1 and 2 uses by evaluating apical transportation, working length loss, and working time in a manikin model.

METHODS
Mesial canals of 40 extracted first mandibular molars were instrumented. Radiographs taken after instrumentation with #25, #30, #35, and #40 files were superimposed on the preoperative image in both mesiodistal and buccolingual angulations. AutoCAD (Autodesk Inc, San Rafael, CA) was used to measure working length loss and apical transportation at 0, 0.5, and 1 mm from the working length (WL). The working time was measured. Group comparison was analyzed using post hoc Tukey honestly significant difference tests (P < .05).

RESULTS
No significant differences were found in apical transportation, working length loss between K3 and K3XF systems, or between the number of uses. Significant differences were found when canal enlargement was performed to a #35-40 (P < .05). K3 instrumentation performed significantly faster (29.6 ± 15.4) than with the K3XF system (40.2 ± 17.7) (P < .05). No differences were observed in working time when comparing the number of uses.

CONCLUSIONS
K3 and R-phase K3XF rotary systems shaped curved root canals safely with minimal apical transportation, even up to a 40/04 file.

Olivieri|Juan Gonzalo|JG|
Stöber|Eva|E|
García Font|Marc|M|
González|Jose Antonio|JA|
Bragado|Pablo|P|
Roig|Miguel|M|
Duran-Sindreu|Fernando|F|

manikin
increased apical enlargement
K3
K3XF
Apical transportation
R-phase
root canal preparation


Analysis of the Gli-D2 locus identifies a genetic target for simultaneously improving the breadmaking and health-related traits of common wheat.

Abstract: Gliadins are a major component of wheat seed proteins. However, the complex homoeologous Gli-2 loci (Gli-A2, -B2 and -D2) that encode the α-gliadins in commercial wheat are still poorly understood. Here we analyzed the Gli-D2 locus of Xiaoyan 81 (Xy81), a winter wheat cultivar. A total of 421.091 kb of the Gli-D2 sequence was assembled from sequencing multiple bacterial artificial clones, and 10 α-gliadin genes were annotated. Comparative genomic analysis showed that Xy81 carried only eight of the α-gliadin genes of the D genome donor Aegilops tauschii, with two of them each experiencing a tandem duplication. A mutant line lacking Gli-D2 (DLGliD2) consistently exhibited better breadmaking quality and dough functionalities than its progenitor Xy81, but without penalties in other agronomic traits. It also had an elevated lysine content in the grains. Transcriptome analysis verified the lack of Gli-D2 α-gliadin gene expression in DLGliD2. Furthermore, the transcript and protein levels of protein disulfide isomerase were both upregulated in DLGliD2 grains. Consistent with this finding, DLGliD2 had increased disulfide content in the flour. Our work sheds light on the structure and function of Gli-D2 in commercial wheat, and suggests that the removal of Gli-D2 and the gliadins specified by it is likely to be useful for simultaneously enhancing the end-use and health-related traits of common wheat. Because gliadins and homologous proteins are widely present in grass species, the strategy and information reported here may be broadly useful for improving the quality traits of diverse cereal crops.

Li|Da|D|
Jin|Huaibing|H|
Zhang|Kunpu|K|
Wang|Zhaojun|Z|
Wang|Faming|F|
Zhao|Yue|Y|
Huo|Naxin|N|
Liu|Xin|X|
Gu|Yong Q|YQ|0000-0002-2575-4744
Wang|Daowen|D|
Dong|Lingli|L|

D001939:Bread
D020869:Gene Expression Profiling
D017343:Genes, Plant
D056426:Genetic Loci
D005903:Gliadin
D009753:Nutritive Value
D010940:Plant Proteins
D019655:Quantitative Trait, Heritable
D014908:Triticum

health-related trait
wheat
gliadin
breadmaking quality
lysine content
transcriptome analysis
protein disulfide isomerase


Electrospun nanofibers as a bioadhesive platform for capturing adherent leukemia cells.

Abstract: This study investigated the adhesive behaviors of normal and abnormal hematopoietic cells on nanotopographical materials. Previously, electrospun nanofiber scaffolds (NFSs) were used to capture and expand hematopoietic stem cells in vitro; here, we demonstrate that NFS could also serve as a useful bioadhesive platform for capturing functionally adherent leukemia cells. Collagen-blended poly(d,l-lactide-co-glycolide) NFS enabled more rapid and efficient capture of K562 leukemia cells than tissue culture polystyrene surfaces with up to 70% improved adhesion and shorter time. Cellular extensions, stronger adhesion, and enhanced cell-cell interactions were observed in K562 cells captured on NFS. While NFS promoted hematopoietic progenitor cell proliferation, it inhibited leukemia cell proliferation and affected cell cycle status by shifting more cells toward the G0/G1 phase. The expression of α-integrins was equally high in both captured and uncaptured leukemia cell populations demonstrating no relation to its adhesive nature. Hematopoietic morphological signatures of NFS captured cells presented no impact on cell differentiation. We conclude that electrospun NFS serves as an excellent platform not only for capturing functionally adherent leukemia cells but also for studying the impact of niche-like structure in the nanoscale.

Cao|Xue|X|
Kwek|Kenneth|K|
Chan|Jerry K Y|JK|
Chan|Casey K H|CK|
Lim|Mayasari|M|

D015973:Gene Expression Regulation, Leukemic

biomimetic scaffold
electrospinning
extracellular matrix
hematopoietic cell adhesion
nanotopography


RAAS, ACE2 and COVID-19; a mechanistic review.

Abstract: The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) patients has been claimed as associated with the risk of COVID-19 infection and its subsequent morbidities and mortalities. These claims were resulting from the possibility of upregulating the expression of angiotensin-converting enzyme 2 (ACE2), facilitation of SARS-CoV-2 entry, and increasing the susceptibility of infection in such treated cardiovascular patients. ACE2 and renin-angiotensin-aldosterone system (RAAS) products have a critical function in controlling the severity of lung injury, fibrosis, and failure following the initiation of the disease. This review is to clarify the mechanisms beyond the possible deleterious effects of angiotensin II (Ang II), and the potential protective role of angiotensin 1-7 (Ang 1-7) against pulmonary fibrosis, with a subsequent discussion of the latest updates on ACEIs/ARBs use and COVID-19 susceptibility in the light of these mechanisms and biochemical explanation.

Elshafei|Ahmed|A|
Khidr|Emad Gamil|EG|
El-Husseiny|Ahmed A|AA|
Gomaa|Maher H|MH|

ACEIs, angiotensin-converting enzyme inhibitors

AEC-II, alveolar epithelial type II cells

ERK, extracellular signal-regulated kinase

NLRP3, (NOD, LRR, and pyrin domain-containing protein 3)

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


Impact of Vitamin D Supplementation on Semen Quality in Vitamin D-Deficient Infertile Males with Oligoasthenozoospermia.

Abstract:
Introduction
Male factor contributes to almost 50% cases of infertility. There is evidence of the effect of serum vitamin D on male fertility by helping in spermatozoa maturation and initiating acrosomal reaction. In India, vitamin D deficiency has been documented to be in the range of 50-90% among all the age groups.

Objective
To study the levels of vitamin D and the impact of vitamin D supplementation in vitamin D-insufficient/deficient infertile males with oligoasthenozoospermia.

Material and methods
This study is a longitudinal observation study. Infertile men with either oligozoospermia or asthenozoospermia with vitamin D levels < 30 ng/ml were enrolled. Vitamin D and calcium supplementation was given, and semen and hormone parameters were assessed at the end of 3 and 6 months.

Result
There is significant improvement in the mean sperm concentration and progressive sperm motility in infertile males with oligoasthenozoospermia after 6 months of vitamin D supplementation (p value < 0.001). The overall clinical pregnancy rate in the study was 8.33% after vitamin D supplementation (p value 0.24).

Conclusion
Vitamin D supplementation plays a crucial role in regulating male fertility.

Wadhwa|Leena|L|
Priyadarshini|Srishti|S|
Fauzdar|Ashish|A|
Wadhwa|Sanjana N|SN|
Arora|Sarika|S|

Oligoasthenozoospermia
Vitamin D deficiency
Sperm concentration
Sperm motility
Male infertility


Abstract: Oxidative stress is a leading cause of endothelial dysfunction. The p38 MAPK pathway plays a determinant role in allowing cells to cope with oxidative stress and is tightly regulated by a balanced interaction between p38 protein and its interacting partners. By using a proteomic approach, we identified nucleophosmin (NPM) as a new partner of p38 in HUVECs. Coimmunoprecipitation and microscopic analyses confirmed the existence of a cytosolic nucleophosmin (NPM)/p38 interaction in basal condition. Oxidative stress, which was generated by exposure to 500 µM H2O2, induces a rapid dephosphorylation of NPM at T199 that depends on phosphatase PP2A, another partner of the NPM/p38 complex. Blocking PP2A activity leads to accumulation of NPM-pT199 and to an increased association of NPM with p38. Concomitantly to its dephosphorylation, oxidative stress promotes translocation of NPM to the nucleus to affect the DNA damage response. Dephosphorylated NPM impairs the signaling of oxidative stress-induced DNA damage via inhibition of the phosphorylation of ataxia-telangiectasia mutated and DNA-dependent protein kinase catalytic subunit. Overall, these results suggest that the p38/NPM/PP2A complex acts as a dynamic sensor, allowing endothelial cells to react rapidly to acute oxidative stress.-Guillonneau, M., Paris, F., Dutoit, S., Estephan, H., Bénéteau, E., Huot, J., Corre, I. Oxidative stress disassembles the p38/NPM/PP2A complex, which leads to modulation of nucleophosmin-mediated signaling to DNA damage response.

Guillonneau|Maëva|M| Paris|François|F| Dutoit|Soizic|S| Estephan|Hala|H| Bénéteau|Elise|E| Huot|Jacques|J| Corre|Isabelle|I|

D015971:Gene Expression Regulation, Enzymologic

D048051:p38 Mitogen-Activated Protein Kinases

endothelial dysfunction
p38 MAPK
phosphatases
double-strand breaks
reactive oxygen species


Acute effects of walking in water on vascular endothelial function and heart rate variability in healthy young men.

Abstract:
AIM
Aquatic exercise might improve endothelial function due to hydrostatic pressure increasing blood flow and causing shear stress to the endothelium. However, the acute effect of aerobic exercise in water on endothelial function is unclear. The present study compares the acute effect of aerobic exercise at moderate intensity in water and on land on endothelial function.

METHODS
Nine healthy young men walked on a treadmill for 30 min while immersed in water up to the xiphoid at 30.0 ± 0.2°C and on land at an intensity equivalent to 60% heart rate reserve in a crossover trial. Brachial artery flow-mediated dilation (FMD) was measured at baseline and at 30 and 60 min after exercise. Autonomic nervous activity was compared among conditions at the heart rate variability (HRV) during exercise.

RESULTS
FMD significantly decreased at 30 min after exercise on land trial (p < 0.05), but did not change after the aquatic trial. However, FMD was significantly higher after aquatic trial than land trial (p < 0.05) at 30 and 60 min after exercise, whereas heart rate, blood pressure, and HRV did not significantly differ between them.

CONCLUSION
These findings demonstrate that aerobic exercise in water suppressed the decrease in FMD compared with that on land, regardless of autonomic nervous activity.

endothelial function
heart rate variability
aquatic exercise
Aerobic exercise
vasodilation


Systemic administration of a fibroblast growth factor receptor 1 agonist rescues the cognitive deficit in aged socially isolated rats.

Abstract: Social isolation predominantly occurs in elderly people and it is strongly associated with cognitive decline. However, the mechanisms that produce isolation-related cognitive dysfunction during aging remain unclear. Here, we evaluated the cognitive, electrophysiological, and morphological effects of short- (4 weeks) and long-term (12 weeks) social isolation in aged male Wistar rats. Long-term but not short-term social isolation increased the plasma corticosterone levels and impaired spatial memory in the Morris water maze. Moreover, isolated animals displayed dampened hippocampal long-term potentiation in vivo, both in the dentate gyrus (DG) and CA1, as well as a specific reduction in the volume of the stratum oriens and spine density in CA1. Interestingly, social isolation induced a transient increase in hippocampal basic fibroblast growth factor (FGF2), whereas fibroblast growth factor receptor 1 (FGFR1) levels only increased after long-term isolation. Importantly, subchronic systemic administration of FGL, a synthetic peptide that activates FGFR1, rescued spatial memory in long-term isolated rats. These findings provide new insights into the neurobiological mechanisms underlying the detrimental effects on memory of chronic social isolation in the aged.

Pereda-Pérez|Inmaculada|I|
Valencia|Azucena|A|
Baliyan|Shishir|S|
Núñez|Ángel|Á|
Sanz-García|Ancor|A|
Zamora|Berta|B|
Rodríguez-Fernández|Raquel|R|
Esteban|José Antonio|JA|
Venero|César|C|

D051496:Receptor, Fibroblast Growth Factor, Type 1

Cognition Corticosterone FGF Hippocampus LTP Stress


Impact of a Carbohydrate Mouth Rinse on Corticomotor Excitability after Mental Fatigue in Healthy College-Aged Subjects.

Abstract:
Mental Fatigue (MF) has been associated with reduced physical performance but the mechanisms underlying this result are unclear. A reduction in excitability of the corticomotor system is a way mental fatigue could negatively impact physical performance. Carbohydrate (CHO) mouth rinse (MR) has been shown to increase corticomotor excitability.

PURPOSE
The purpose of this study was to determine if CHO MR impacts corticomotor excitability after MF.

METHODS
Fifteen subjects (nine females, six males; age = 23 ± 1 years; height = 171 ± 2 cm; body mass = 69 ± 3 kg; BMI = 23.8 ± 0.7) completed two sessions under different MR conditions (Placebo (PLAC), 6.4% glucose (CHO)) separated by at least 48 h and applied in a double-blinded randomized fashion. Motor-evoked potential (MEP) of the left first dorsal interosseous (FDI) was determined by transcranial magnetic stimulation (TMS) before and after MF. Perceived MF was recorded before and after the MF task using a 100 mm visual analog scale (VAS).

RESULTS
MF was greater following PLAC (+30.4 ± 4.0 mm) than CHO (+19.4 ± 3.9 mm) (p = 0.005). MEP was reduced more following PLAC (-16.6 ± 4.4%) than CHO (-3.7 ± 4.7%) (p < 0.001).

CONCLUSIONS
CHO MR was successful at attenuating the reduction in corticomotor excitability after MF. Carbohydrate mouth rinse may be a valuable tool at combating the negative consequences of mental fatigue.

Bailey|Stephen P|SP|
Harris|G Keith|GK|0000-0002-3424-1836
Lewis|Kaitlin|K|
Llewellyn|Tracy A|TA|
Watkins|Ruth|R|
Weaver|Mark A|MA|
Roelands|Bart|B|0000-0002-2808-044X
Van Cutsem|Jeroen|J|
Folger|Stephen F|SF|


Intimate partner violence as a factor associated with risky sexual behaviours and alcohol misuse amongst men in South Africa.

Abstract: Globally intimate partner violence (IPV) is a public health problem that can be perpetrated by both males and females, although males are more likely to inflict severe IPV-related injuries on their female partners. In low- and middle-income countries like South Africa, few studies have conducted research to determine whether IPV perpetration by men may be a risk factor for engaging in other risk behaviours. The aim of this study is to determine whether IPV perpetration by men is a risk factor for engaging in other risk behaviours with a particular focus on risky sexual behaviours and alcohol misuse. The data for this study were drawn from a multilevel intervention study, which addressed the nexus of alcohol abuse and HIV prevention among men in South Africa. Men were screened and recruited from informal drinking places within 12 communities situated in one of the oldest, predominantly Xhosa-speaking African townships in Cape Town. Univariate and multivariate logistic regression models were used to analyse the associations between IVP and potential explanatory variables. Of the 975 men included in the survey, 39.9% reported to have been involved in Intimate Partner Violence. IPV perpetration was significantly more likely among men who reported having a child [OR 1.51 (1.07-2.14) p = .019], having a casual sexual partner [OR 1.51 (1.11-2.05) p = .008], and those with possible alcohol dependence [OR 3.46 (1.17-10.20) p = .024]. IPV was significantly less likely among men with matric educational qualification than those with no education [OR 0.30 (95% CI: 0.09-1.02) p = .053] and among those who reported using a condom at last sex [OR 0.69 (0.50-0.97) p = .034]. We therefore recommend that interventions aimed at reducing IPV need to address risky sexual and drinking behaviours amongst men simultaneously, while also focusing on intimate relationship power dynamics and gendered norms amongst couples.

Mthembu|J C|JC|
Khan|G|G|
Mabaso|M L H|ML|
Simbayi|L C|LC|

Intimate partner violence
risky sexual behaviour
alcohol misuse
HIV
gender


Metal resistance genes enrichment in marine biofilm communities selected by biocide-containing surfaces in temperate and tropical coastal environments.

Abstract: Microorganisms able to form biofilms in marine ecosystems are selected depending on immersed surfaces and environmental conditions. Cell attachment directly on toxic surfaces like antifouling coatings suggests a selection of tolerant (or resistant) organisms with characteristics conferring adaptive advantages. We investigated if environment would drive metal resistance gene abundance in biofilms on artificial surfaces. Biofilms were sampled from three surfaces (a PVC reference and two antifouling coatings) deployed in three coastal waters with dissimilar characteristics: The Mediterranean Sea (Toulon) and Atlantic (Lorient) and Indian (Reunion) Oceans. The two coatings differed in metals composition, either Cu thiocyanate and Zn pyrithione (A3) or Cu2O (Hy). Metal resistance genes (MRG) specific to copper (cusA, copA, cueO) or other metals (czcA and pbrT) were monitored with qPCR in parallel to the microbial community using 16S rRNA gene metabarcoding. A lower α-diversity on A3 or Hy than on PVC was observed independent on the site. Weighted Unifrac suggested segregation of communities primarily by surface, with lower site effect. Metacoder log2 fold change ratio and LeFSe discrimination suggested Marinobacter to be specific of Hy and Altererythrobacter, Erythrobacter and Sphingorhabdus of A3. Likewise, the relative abundance of MRG (MRG/bacterial 16S rRNA) varied between surfaces and sites. A3 presented the greatest relative abundances for cusA, cueO and czcA. The latter could only be amplified from A3 communities, except at Toulon. Hy surface presented the highest relative abundance for copA, specifically at Lorient. These relative abundances were correlated with LeFSe discriminant taxa. Dasania correlated positively with all MRG except cueO. Marinobacter found in greater abundance in Hy biofilm communities correlated with the highest abundances of copA and Roseovarius with czcA. These results prove the selection of specific communities with abilities to tolerate metallic biocides forming biofilms over antifouling surfaces, and the secondary but significant influence of local environmental factors.

Catao|Elisa C P|ECP|
Gallois|Nicolas|N|
Fay|Fabienne|F|
Misson|Benjamin|B|
Briand|Jean-François|JF|

Antifouling surface
Anthropogenic effect
Complex communities
Copper tolerance


Investigation of the Potential Use of Calcium Alginate Capsules for Self-Healing in Porous Asphalt Concrete.

Abstract: Improving the healing capacity of asphalt is proving to be an effective method to prolong the service life of an asphalt pavement. The calcium alginate capsules encapsulating rejuvenator have been developed and proved to provide successful localized crack healing in asphalt mastic. However, it is not known whether this self-healing asphalt system will improve healing capacity of a full asphalt mix. To this aim, this paper reports on study which investigate effect of the calcium alginate capsules onto self-healing capacity of the porous asphalt mix. X-ray computed tomography (XCT) was used to visualize the distribution of the capsules in porous asphalt. The effect of the capsules on fracture resistance of porous asphalt concrete was studied by semi-circular bending (SCB) tests. A semi-circular bending and healing programme was carried out to evaluate the healing effect of these capsules in porous asphalt concrete. Indirect Tensile Stiffness Modulus (ITSM) tests were employed in order to investigate the influence of the capsules on the stiffness of the porous asphalt concrete. The results indicate that incorporating calcium alginate capsules significantly improve the healing capacity of porous asphalt concrete without compromising its performance.

calcium alginate capsules
self-healing
asphalt
rejuvenation


1.0 s Ultrafast MRI in non-sedated infants after reduction with spica casting for developmental dysplasia of the hip: a feasibility study.

Abstract:
PURPOSE
The aim of this study was to first develop and use 1.0 s ultrafast magnetic resonance imaging (MRI) to confirm the location of the femoral head in non-sedated infants with developmental dysplasia of the hip (DDH) after reduction with spica cast application in clinical settings.

METHODS
The ultrafast acquisition was achieved by employing a balanced steady-state free precession sequence and immobilizing the patient with dedicated sandbags. On completion of the ultrafast MRI study, all infants were sedated for conventional MRI scanning. Two orthopaedic surgeons retrospectively evaluated the image quality, result of the reduction and total MRI study time (including patient immobilization, coil setup, and scanning) in 14 DDHs of 13 infants (one with bilateral DDHs).

RESULTS
Both reviewers stated that there were no motion artefacts for non-sedated infants during the ultrafast MRI and that the quality of both the ultrafast and conventional MRI images were acceptable to assess the femoral head location. Assessment of the reduction procedure resulted in two hips being categorized as 'incomplete reduction' requiring a re-reduction procedure. The total study time of ultrafast and conventional MRI was 6 ± 1 min and 14 ± 3 min, respectively (P < 0.001). No complications due to sedation, such as hypoxia, were reported. The average sedation waiting time was 1 h 25 min ± 34 min.

CONCLUSION
The ultrafast MRI procedure reported here can be readily employed to confirm the location of the femoral head in infants with DDHs, without the use of any sedation.

Fukuda|Atsushi|A| Fukiage|Kenichi|K| Futami|Tohru|T| Miyati|Tosiaki|T|

Reduction
Spica casting
Developmental dysplasia of the hip
Ultrafast magnetic resonance imaging
Femoral head location


Binding of CLL subset 4 B-cell receptor immunoglobulins to viable human memory B lymphocytes requires a distinctive IGKV somatic mutation.

Abstract: Amino acid replacement mutations in certain CLL stereotyped B-cell receptor (BCR) immunoglobulins (IGs) at defined positions within antigen-binding sites strongly imply antigen selection. Prime examples of this are CLL subset 4 BCR IGs using IGHV4-34/IGHD5-18/IGHJ6 and IGKV2-30/IGKJ2 rearrangements. Conspicuously and unlike most CLL IGs, subset 4 IGs do not bind apoptotic cells. By testing the (auto)antigenic reactivities of subset 4 IGs toward viable lymphoid-lineage cells and specific autoantigens typically bound by IGHV4-34+ IGs, we found IGs from both subset 4 and non-subset 4 IGHV4-34-expressing CLL cases bind naïve B cells. However, only subset 4 IGs react with memory B cells. Furthermore, subset 4 IGs do not bind DNA nor i or I carbohydrate antigens, common targets of IGHV4-34-utilizing antibodies in systemic lupus erythematosus and cold agglutinin disease, respectively. Notably, we found that subset 4 IG binding to memory B lymphocytes depends on an aspartic acid at position 66 of FR3 in the rearranged IGKV2-30 gene; this amino acid residue is acquired by somatic mutation. Our findings illustrate the importance of positive and negative selection criteria for structural elements in CLL IGs and suggest that autoantigens driving normal B cells to become subset 4 CLL cells differ from those driving IGHV4-34+ B cells in other diseases.

Catera|Rosa|R|
Liu|Yun|Y|
Gao|Chao|C|
Yan|Xiao-Jie|XJ|
Magli|Amanda|A|
Allen|Steven L|SL|
Kolitz|Jonathan E|JE|
Rai|Kanti R|KR|
Chu|Charles C|CC|
Feizi|Ten|T|
Stamatopoulos|Kostas|K|
Chiorazzi|Nicholas|N|

stereotyped B-cell receptor
memory B cells
CD10 antigen
VK mutation
chronic lymphocytic leukemia


Anxiety comorbidity in schizophrenia.

Abstract: Diagnostic and treatment hierarchical reductionisms have led to an oversight of anxiety syndromes in schizophrenia. Nevertheless, recent data have indicated that anxiety can be a significant source of morbidity in this patient group. This paper reviews current knowledge concerning anxiety comorbidity in schizophrenia, its epidemiology, course, and treatment. A computerized search of the literature published from 1966 to July 2012 was conducted on Medline. Comorbid anxiety disorders are present in 38.3% of subjects with schizophrenia spectrum disorders. The most common anxiety disorder is social phobia followed by post-traumatic stress disorder and obsessive compulsive disorder. The presence and severity of symptoms of anxiety are associated with more severe clinical features and poorer outcomes. Available literature on the treatment consists primarily of case reports and open trials. Fragments of data support the notion of treating these anxiety states and syndromes as co-occurring clinical conditions with adjunctive medications and psychosocial interventions. However, additional work remains to be done on this issue before firm conclusions can be drawn.

Braga|Raphael J|RJ|
Reynolds|Graham P|GP|
Siris|Samuel G|SG|

Anxiety Comorbidity Schizophrenia Review


Mindful Connections: The Role of a Peer Support Group on the Psychosocial Adjustment for Adults Recovering From Brain Injury.

Abstract: How does participating in a peer support group impact an adult's psychosocial adjustment following brain injury? This question was investigated using a qualitative approach, interviewing patients recruited from an ambulatory care program. Data analysis guided by Bury's sociological framework, biographical disruption and biographical repair, revealed participants' pregroup disrupted sense of self, including subthemes related to intrinsic losses and uncertainty. Enhanced psychosocial adjustment including subthemes described participants' reorientation through shared experience. Finally, a postgroup adapted sense of self including subthemes was characterized by heightened purpose, self-awareness, and acceptance. Findings lend weight to using tailored peer interventions to optimize psychosocial adjustment for this population.

Cutler|Melissa|M|
Nelson|Michelle L A|MLA|
Nikoloski|Maya|M|
Kuluski|Kerry|K|

psychosocial
qualitative
Acquired brain injury
disability frameworks
mental health recovery
neurorehabilitation
peer group
stroke


Glucocorticoids mediate circadian timing in peripheral osteoclasts resulting in the circadian expression rhythm of osteoclast-related genes.

Abstract: Circadian rhythms are prevalent in bone metabolism. However, the molecular mechanisms involved are poorly understood. Recently, we suggested that output signals from the suprachiasmatic nucleus (SCN) are transmitted from the master circadian rhythm to peripheral osteoblasts through β-adrenergic and glucocorticoid signaling. In this study, we examined how the master circadian rhythm is transmitted to peripheral osteoclasts and the role of clock gene in osteoclast. Mice were maintained under 12-hour light/dark periods and sacrificed at Zeitgeber times 0, 4, 8, 12, 16 and 20. mRNA was extracted from femur (cancellous bone) and analyzed for the expression of osteoclast-related genes and clock genes. Osteoclast-related genes such as cathepsin K (CTSK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) showed circadian rhythmicity like clock genes such as period 1 (PER1), PER2 and brain and muscle Arnt-like protein 1 (BMAL1). In an in vitro study, not β-agonist but glucocorticoid treatment remarkably synchronized clock and osteoclast-related genes in cultured osteoclasts. Chromatin immunoprecipitation (ChIP) assay showed the interaction between BMAL1 proteins and promoter region of CTSK and NFATc1. To examine whether endogenous glucocorticoids influence the osteoclast circadian rhythms, mice were adrenalectomized (ADX) and maintained under 12-hour light/dark periods at least two weeks before glucocorticoid injection. A glucocorticoid injection restarted the circadian expression of CTSK and NFATc1 in ADX mice. These results suggest that glucocorticoids mediate circadian timing to peripheral osteoclasts and osteoclast clock contributes to the circadian expression of osteoclast-related genes such as CTSK and NFATc1.

Fujihara|Yuko|Y| Kondo|Hisataka|H| Noguchi|Toshihide|T| Togari|Akifumi|A|

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction

Glucocorticoid
Osteoclast
Circadian rhythm
Clock gene


Content Analysis of Virtual Reference Data: Reshaping Library Website Design.

Abstract: An academic health sciences library wanted to redesign its website to provide better access to health information in the community. Virtual reference data were used to provide information about user searching behavior. This study analyzed three years (2012-2014) of virtual reference data, including e-mail questions, text messaging, and live chat transcripts, to evaluate the library website for redesigning, especially in areas such as the home page, patrons' terminology, and issues prompting patrons to ask for help. A coding system based on information links in the current library website was created to analyze the data.

Fan|Suhua Caroline|SC|
Welch|Jennifer M|JM|

virtual reference
website design
Evidence-based study
statistics
user-friendly website


Out of Asia: the independent rise and global spread of fluoroquinolone-resistant Shigella.

Abstract: Shigella are ranked among the most prevalent aetiologies of diarrhoeal disease worldwide, disproportionately affecting young children in developing countries and high-risk communities in developed settings. Antimicrobial treatment, most commonly with fluoroquinolones, is currently recommended for Shigella infections to alleviate symptoms and control disease transmission. Resistance to fluoroquinolones has emerged in differing Shigella species (S. dysenteriae, flexneri and sonnei) since the turn of the 21st century, originating in endemic areas, and latterly spreading into non-endemic regions. Despite occurring independently, the emergence of fluoroquinolone resistance in these different Shigella species shares striking similarities regarding their epidemiology and resistance mechanisms. Here, we review and discuss the current epidemiology of fluoroquinolone-resistant Shigella species, particularly in the light of recent genomic insights.

quinolone resistance determining region (QRDR)


Neurotherapeutic and antioxidant response of D-ribose-L-Cysteine nutritional dietary supplements on Alzheimer-type hippocampal neurodegeneration induced by cuprizone in adult male wistar rat model.

Abstract:
INTRODUCTION
Cuprizone is a neurotoxicant causing neurodegeneration through enzymes inhibition and oxidative stress. D-Ribose-L-Cysteine (DRLC) is a powerful antioxidant with neuroprotective properties. This study explored the antioxidant response of DRLC against cuprizone-induced behavioral alterations, biochemical imbalance and hippocampal neuronal damage in adult wistar rats.

MATERIALS AND METHODS
Thirty two (32) adult male wistar rats (150-200g) were divided into four groups (n = 8). Group A received normal saline only as placebo; Group B received 0.5% cuprizone diet only; Group C received a combination of 0.5% cuprizone diet and 100 mg/kg bw of DRLC and Group D received 100 mg/kg bw of DRLC only. The administration was done through oral gavage once daily for 45 days. After the last treatment, neurobehavioral tests (Morris Water Maze and Y maze) was conducted; animals sacrificed and brain harvested for histological analysis and biochemical estimations of levels of antioxidants, oxidative stress markers, neurotransmitters and enzyme activitties.

RESULTS
The results showed significant memory decline, hippocampal alterations, decrease levels of antioxidant markers, enzyme and neurotransmitters activities with concomitant increase in norepinephrine and oxidative stress markers in cuprizone induced rats relative to normal but was attenuated with DRLC administration.

CONCLUSION
Cuprizone causes cognitive impairment and neurodegeneration through oxidative stress; however, administration of DRLC ameliorated neuropathological alteration induced by cuprizone.

Ogunlade|B|B|
Fidelis|O P|OP|
Afolayan|O O|OO|
Agie|J A|JA|

D-ribose-L-cysteine
Cuprizone
Oxidative stress
Memory and hippocampus


Practicality of Acute and Transitional Care and its consequences in the era of SwissDRG: a focus group study.

Abstract:
BACKGROUND
Switzerland recently introduced Acute and Transitional Care (ATC) as a new financing option and a preventive measure to mitigate potential side effects of Swiss Diagnosis Related Group (SwissDRG). The goal of ATC was to support patients who after acute treatment at a hospital require temporary increased professional care. However, evidence is lacking as to the practicality of ATC.

METHODS
Using qualitative focus group methodology, we sought to understand the implementation and use of ATC. A purposive sample of forty-two professionals from five Swiss cantons participated in this study. We used a descriptive thematic approach to analyse the data.

RESULTS
Our findings first reveal that ATC's implementation differs in the five cantons (i.e. federal states). In two cantons, only ambulatory variant of ATC is used; in one canton only stationary ATC has been created, and two cantons had both ambulatory and stationary ATC but preferred the latter. Second, there are intrinsic practical challenges associated with ATC, which include physicians' lack of familiarity with ATC and its regulatory limitations. Finally, participants felt that due to shorter hospital stays because of SwissDRG, premature discharge of patients with complex care needs to stationary ATC takes place. This development does not fit the nursing home concept of care tailored to long-term patients.

CONCLUSION
This empirical study underscores that there is a strong need to improve ATC so that it is uniformly implemented throughout the country and its application is streamlined. In light of the newness of ATC as well as SwissDRG, their impact on the quality of care received by patients is yet to be fully understood. Empirical evidence is necessary to improve these two measures.

Wangmo|Tenzin|T|
Padrutt|Yvonne|Y|
Koné|Insa|I|
Gächter|Thomas|T|
Elger|Bernice S|BS|
Leu|Agnes|A|

D003953:Diagnosis-Related Groups
D004632:Emergency Medical Services
D005069:Evaluation Studies as Topic
D017144:Focus Groups
D006801:Humans
D011446:Prospective Studies
D013557:Switzerland
D000069341:Transitional Care

Acute and transitional care
SwissDRG
Switzerland
ATC
DRG
Health policy


A machine learning-based risk stratification model for ventricular tachycardia and heart failure in hypertrophic cardiomyopathy.

Abstract:
BACKGROUND
Machine learning (ML) and artificial intelligence are emerging as important components of precision medicine that enhance diagnosis and risk stratification. Risk stratification tools for hypertrophic cardiomyopathy (HCM) exist, but they are based on traditional statistical methods. The aim was to develop a novel machine learning risk stratification tool for the prediction of 5-year risk in HCM. The goal was to determine if its predictive accuracy is higher than the accuracy of the state-of-the-art tools.

METHOD
Data from a total of 2302 patients were used. The data were comprised of demographic characteristics, genetic data, clinical investigations, medications, and disease-related events. Four classification models were applied to model the risk level, and their decisions were explained using the SHAP (SHapley Additive exPlanations) method. Unwanted cardiac events were defined as sustained ventricular tachycardia occurrence (VT), heart failure (HF), ICD activation, sudden cardiac death (SCD), cardiac death, and all-cause death.

RESULTS
The proposed machine learning approach outperformed the similar existing risk-stratification models for SCD, cardiac death, and all-cause death risk-stratification: it achieved higher AUC by 17%, 9%, and 1%, respectively. The boosted trees achieved the best performing AUC of 0.82. The resulting model most accurately predicts VT, HF, and ICD with AUCs of 0.90, 0.88, and 0.87, respectively.

CONCLUSIONS
The proposed risk-stratification model demonstrates high accuracy in predicting events in patients with hypertrophic cardiomyopathy. The use of a machine-learning risk stratification model may improve patient management, clinical practice, and outcomes in general.

Smole|Tim|T|
Žunkovič|Bojan|B|
Pičulin|Matej|M|
Kokalj|Enja|E|
Robnik-Šikonja|Marko|M|
Kukar|Matjaž|M|
Fotiadis|Dimitrios I|DI|
Pezoulas|Vasileios C|VC|
Tachos|Nikolaos S|NS|
Barlocco|Fausto|F|
Mazzarotto|Francesco|F|
Popović|Dejana|D|
Maier|Lars|L|
Velicki|Lazar|L|
MacGowan|Guy A|GA|
Olivotto|Iacopo|I|
Filipović|Nenad|N|
Jakovljević|Djordje G|DG|
Bosnić|Zoran|Z|

D001185:Artificial Intelligence
D002312:Cardiomyopathy, Hypertrophic
D006333:Heart Failure
D006801:Humans
D000069550:Machine Learning
D018570:Risk Assessment
D012307:Risk Factors
D017180:Tachycardia, Ventricular

Risk stratification
Hypertrophic cardiomyopathy
Machine learning
Artificial intelligence


Bayesian pedigree inference with small numbers of single nucleotide polymorphisms via a factor-graph representation.

Abstract: We develop a computational framework for addressing pedigree inference problems using small numbers (80-400) of single nucleotide polymorphisms (SNPs). Our approach relaxes the assumptions, which are commonly made, that sampling is complete with respect to the pedigree and that there is no genotyping error. It relies on representing the inferred pedigree as a factor graph and invoking the Sum-Product algorithm to compute and store quantities that allow the joint probability of the data to be rapidly computed under a large class of rearrangements of the pedigree structure. This allows efficient MCMC sampling over the space of pedigrees, and, hence, Bayesian inference of pedigree structure. In this paper we restrict ourselves to inference of pedigrees without loops using SNPs assumed to be unlinked. We present the methodology in general for multigenerational inference, and we illustrate the method by applying it to the inference of full sibling groups in a large sample (n=1157) of Chinook salmon typed at 95 SNPs. The results show that our method provides a better point estimate and estimate of uncertainty than the currently best-available maximum-likelihood sibling reconstruction method. Extensions of this work to more complex scenarios are briefly discussed.

Sum-Product algorithm
Full-sibling reconstruction
Multigeneration pedigree inference
Relationship inference


Maternal age at menarche and offspring body mass index in childhood.

Abstract:
BACKGROUND
Earlier age of menarche has been associated with an increased risk of chronic diseases during adulthood, but whether early menarche has intergenerational effect is not clear.

METHODS
In this population-based cross-sectional study, we recruited children from 26 primary schools using cluster random probability sampling in Shanghai, China, in 2014. We used multiple linear regression models to estimate the adjusted associations of maternal age of menarche (MAM) with offspring body mass index (BMI). We also used the mediation analysis to examine the contribution of maternal BMI and gestational diabetes to offspring BMI.

RESULTS
A total of 17,571 children aged 6-13 years were enrolled, of whom 16,373 had their weight and height measured. Earlier MAM was associated with higher child BMI in boys (- 0.05 z-score per year older MAM, 95% CI - 0.08 to - 0.02) and in girls (- 0.05 z-score per year older MAM, 95% CI - 0.07 to - 0.02). Maternal BMI positively mediated the association of MAM with offspring BMI in both sexes, with mediation effects of 37.7 and 19.4% for boys and girls, respectively.

CONCLUSION
Early maternal menarche was associated with greater offspring BMI. This study provides evidence for the intergenerational effect in the development of BMI in offspring.

Wang|Hui|H| Zhang|Yunting|Y| Tian|Ying|Y| Li|Fei|F| Yan|Chonghui|C| Wang|Hui|H| Luo|Zhongchen|Z| Jiang|Fan|F| Zhang|Jun|J|

Body mass index
Early menarche
Intergenerational study


Interactions of established risk factors and a GWAS-based genetic risk score on the risk of venous thromboembolism.

Abstract: Multiple genetic and environmental risk factors contribute to venous thromboembolism (VTE) risk. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of VTE and may identify opportunities for targeted prevention and treatment. It was our aim to examine the main effects and the potential effect-modification between single nucleotide polymorphisms (SNPs) at established loci and lifestyle risk factors for VTE. We performed a nested case-control study using data on 1,040 incident VTE cases and 16,936 controls from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood, were selected as participants in a previous genome-wide association study (GWAS), and completed a biennial questionnaire at time of blood draw. We selected SNPs that were associated with VTE risk in previous GWAS studies. A genetic risk score (GRS) was constructed to evaluate the combined effect of the 16 SNPs that have reached genome-wide significance in previous GWAS of VTE. Interactions between SNPs and VTE risk factors (BMI and smoking) were also assessed. We found a significant association between our GRS and VTE risk. The risk of VTE among individuals in the highest GRS tertile was 2.02 times that of individuals in the lowest GRS tertile (p-trend = 9.69×10(-19)). The OR was 1.52 (p=1.03×10(-8)) for participants in the highest GRS tertile compared to those in the medium GRS tertile. However, while BMI and smoking were associated with VTE, and their effects were additive to each other we did not observe any significant multiplicative gene-environment interactions.

Crous-Bou|Marta|M|
De Vivo|Immaculata|I|
Camargo|Carlos A|CA|
Varraso|Raphaëlle|R|
Grodstein|Francine|F|
Jensen|Majken K|MK|
Kraft|Peter|P|
Goldhaber|Samuel Z|SZ|
Lindström|Sara|S|
Kabrhel|Christopher|C|

D020022:Genetic Predisposition to Disease

venous thromboembolism
smoking
gene-environment interactions
Body mass index
genetic susceptibility


Combined extra-/intrathoracic correction of pectus carinatum and other asymmetric chest wall deformities : A novel technique.

Abstract:
OBJECTIVE
Description of a novel technique to surgically correct (asymmetric) pectus carinatum and other chest deformities using a metal bar without fixation to the ribs.

INDICATIONS
Severe thoracic deformity, extensive psychological strain, social isolation, pain and respiratory complaints. Pseudarthrosis or insufficient correction of a thoracic deformity after prior surgery. Distinctive deformities.

CONTRAINDICATIONS
Acute infections. Postoperative intrathoracic scaring in revision cases can be challenging.

SURGICAL TECHNIQUE
One-lung ventilation is used. Through two 3-4 cm long bilateral incisions to the thorax, an introducer is guided into the thorax under thoracoscopic supervision and then guided through an intercostal space out of the thorax again. A 1 cm presternal incision is performed and nylon threads are attached to the introducer bilaterally. Then the preshaped metal bar can be placed following the nylon threads. Once the metal bar is placed, the deformity is instantly corrected. Bilateral stabilizers are fixed with wire cerclage. Fixation on the ribs is not necessary.

POSTOPERATIVE MANAGEMENT
Postoperative thorax x‑ray. Intensive ventilation exercises. Implant removal after 2-3 years.

RESULTS
The technique was used in 10 primary pectus carinatum or combined pectus carinatum and excavatum deformities as well as in 6 revision cases (3 female, 13 male, age 13-32 years). Follow-up ranged from 3-15 months postoperatively. Cosmetic results were excellent. Revision surgery required in 2 patients (one rib fracture and one local implant irritation).

Thorax
Bone diseases, developmental
Costal cartilage
Minimally invasive surgery
Sternum