Looking for an optimal pedal layout to improve the driving performance of patients with diabetic peripheral neuropathy.

Abstract: Diabetes can undermine people's ability to drive safely, but most previous studies have focused on its deterioration of the central nervous system. This study sought to investigate how diabetic peripheral neuropathy (DPN), a common complication of diabetes characterized by reduced sensitivity of the limbs, can influence people's braking behavior and other safety-related measures of driving. In addition, it also tested how such a deteriorating effect can be reduced by using certain pedal layout designs. In total, 29 healthy drivers and 31 drivers of type 2 diabetes matched in demographic variables were invited to participate in this study. The participants with type 2 diabetes (they are from here on out referred to as "patients")were then split into two subgroups based on the severity of DPN using the median of the Semmes-Weinstein monofilaments Examination (SWME) scores. All three groups of participants finished a series of vehicle-pedestrian conflict tasks in a driving simulator using nine different types of pedal layouts. These layouts varied in the lateral distance between the accelerator and the brake (45 mm, 60 mm, and 75 mm) and the width of brake pedals (50 mm, 70 mm, 90 mm). The results showed that patients with serious DPN had longer brake reaction times (BRT) and shorter minimum distance-to-collision (DTC) as compared to the other two groups. However, the effects of such a disadvantage varied across different pedal layouts. When the accelerator-brake distance was 45 mm, patients with serious DPN showed no compromised driving performance as compared to other two groups. In conclusion, we found the DPN could undermine driving performance of participants with type 2 diabetes, and a closer accelerator-brake lateral distance (45 mm) may be an optimal choice for them to counteract such a negative influence.

Ma|Shu|S| Wu|Changxu|C| Zhang|Jingyu|J| Zeng|Xianzhong|X| Zhao|Guozhen|G| Sun|Xianghong|X|

Diabetic peripheral neuropathy
Braking behavior
Pedal layout design
Drivers with type 2 diabetes


On a knife-edge: clinical uncertainty with an extensive knife blade in situ in the craniofacial region.

Abstract: A 25-year-old man presented to the trauma department following a penetrating stab wound to his left infraorbital margin with retained knife blade causing superoposterior displacement of the globe. Plain skull X-ray revealed an extensive retained blade with subsequent CT imaging revealing the tip of the blade had reached the right styloid process with no neurovascular compromise. Initial concern was primarily for the left eye leading to ophthalmology being the first specialty requested to review the patient. However, once the extent of the injury was established, ophthalmology requested further review from maxillofacial, ENT and neurosurgery. This resulted in an 84 hours wait between the initial injury and the removal of the knife blade. Incredibly, the patient had no initial sequelae from such an extensive injury and had an unremarkable recovery with no further complications aside from a laceration to the left inferior rectus muscle that was conservatively managed.

Dai|Dairui|D|
Meyer|Silke|S|
Kaltheuner|Lars Christian|LC|
Plani|Frank|F|

trauma
ophthalmology
emergency medicine
oral and maxillofacial surgery


ZEB1 inhibition sensitizes cells to the ATR inhibitor VE-821 by abrogating epithelial-mesenchymal transition and enhancing DNA damage.

Abstract: The ataxia-telangiectasia-mutated (ATM) and rad3-related (ATR) checkpoint pathway plays an essential role in modulating cellular responses to replication stress and DNA damage to maintain genomic stability. In various tumors, cancer cells have increased dependence on ATR signaling for survival, making ATR a promising target for cancer therapy. ATR inhibitors sensitize multiple tumor cell types to radiation and DNA-damaging agents, but application of an ATR inhibitor alone shows limited efficacy. In the present study, we investigated the role of epithelial-to-mesenchymal transition (EMT) and the EMT transcription factor ZEB1 in regulating cell sensitivity to the ATR inhibitor VE-821. We found that VE-821 induced EMT with concomitant ZEB1 upregulation and promoted migration in cells in which the anti-proliferative effect of VE-821 was limited. Knocking down ZEB1 using siRNA partially reversed VE-821-induced EMT, and sensitized cells to VE-821 via effective attenuation of migration and AKT/ERK signaling. Moreover, ZEB1 inhibition promoted Chk1 phosphorylation and induced S-phase arrest by enhancing TopBP1 expression, which suggests a distinctive modulatory effect of ZEB1 on Chk1. Finally, combining VE-821 with ZEB1 inhibition enhanced DNA damage accumulation. These results demonstrate that EMT represents a novel mechanism for limiting the effectiveness of an ATR inhibitor, and thus suggest that ZEB1 inhibition might represent a new approach to increasing the efficiency of, or reversing resistance to, ATR inhibitors.

Song|Na|N| Jing|Wei|W| Li|Ce|C| Bai|Ming|M| Cheng|Yu|Y| Li|Heming|H| Hou|Kezuo|K| Li|Yanrong|Y| Wang|Kai|K| Li|Zhi|Z| Liu|Yunpeng|Y| Qu|Xiujuan|X| Che|Xiaofang|X|

D064007:Ataxia Telangiectasia Mutated Proteins

D000071799:Zinc Finger E-box-Binding Homeobox 1

ZEB1
sensitivity
ATR
ATR inhibitor
DNA damage
EMT
Chk1


MicroRNA-630 inhibits breast cancer progression by directly targeting BMI1.

Abstract: MicroRNAs (miRNAs) play critical roles in breast cancer cell biological processes, including proliferation and apoptosis by inhibiting the expression of their target genes. Herein, we reported that miR-630 overexpression initiates apoptosis, blocks cell cycle progression and suppresses cell proliferation in breast cancer cells. Furthermore, BMI1, a member of polycomb group family, was identified as a direct target of miR-630, and there was a negative correlation between the expression levels of BMI1 and miR-630 in human breast cancer samples. With a series of biology approaches, subsequently, we proved that BMI1 was a functional downstream target of miR-630 and mediated the property of miR-630-dependent inhibition of breast cancer progression. Taken together, these findings provide further evidence on the tumor-suppression function of miR-630 in breast cancer, and clarify BMI1 as a novel functional target gene of miR-630.

Gong|Xiu-Feng|XF| Yu|An-Lu|AL| Tang|Jun|J| Wang|Chen-Long|CL| He|Jian-Rong|JR| Chen|Guo-Qiang|GQ| Zhao|Qian|Q| He|Ming|M| Zhou|Ci-Xiang|CX|

D015972:Gene Expression Regulation, Neoplastic

D048054:Mitogen-Activated Protein Kinase 7


R3D-BLAST2: an improved search tool for similar RNA 3D substructures.

Abstract:
BACKGROUND
RNA molecules have been known to play a variety of significant roles in cells. In principle, the functions of RNAs are largely determined by their three-dimensional (3D) structures. As more and more RNA 3D structures are available in the Protein Data Bank (PDB), a bioinformatics tool, which is able to rapidly and accurately search the PDB database for similar RNA 3D structures or substructures, is helpful to understand the structural and functional relationships of RNAs.

RESULTS
Since its first release in 2011, R3D-BLAST has become a useful tool for searching the PDB database for similar RNA 3D structures and substructures. It was implemented by a structural-alphabet (SA)-based method, which utilizes an SA with 23 structural letters to encode RNA 3D structures into one-dimensional (1D) structural sequences and applies BLAST to the resulting structural sequences for searching similar substructures of RNAs. In this study, we have upgraded R3D-BLAST to develop a new web server named R3D-BLAST2 based on a higher quality SA newly constructed from a representative and sufficiently non-redundant list of RNA 3D structures. In addition, we have modified the kernel program in R3D-BLAST2 so that it can accept an RNA structure in the mmCIF format as an input. The results of our experiments on a benchmark dataset have demonstrated that R3D-BLAST2 indeed performs very well in comparison to its earlier version R3D-BLAST and other similar tools RNA FRABASE, FASTR3D and RAG-3D by searching a larger number of RNA 3D substructures resembling those of the input RNA.

CONCLUSIONS
R3D-BLAST2 is a valuable BLAST-like search tool that can more accurately scan the PDB database for similar RNA 3D substructures. It is publicly available at http://genome.cs.nthu.edu.tw/R3D-BLAST2/ .

Yen|Ching-Yu|CY|
Lin|Jian-Cheng|JC|
Chen|Kun-Tze|KT|
Lu|Chin Lung|CL|

RNA
BLAST-like search tool
Computational biology
Structural alphabet
Tertiary structure


Digestive exophagy: Phagocyte digestion of objects too large for phagocytosis.

Abstract: Mammalian phagocytes carry out several essential functions, including killing and digesting infectious organisms, clearing denatured proteins, removing dead cells and removing several types of debris from the extracellular space. Many of these functions involve phagocytosis, the engulfment of a target in a specialized endocytic process and then fusion of the new phagosome with lysosomes. Phagocytes such as macrophages can phagocytose targets that are several micrometers in diameter (eg, dead cells), but in some cases they encounter much larger objects. We have studied two such examples in some detail: large deposits of lipoproteins such as those in the wall of blood vessels associated with atherosclerosis, and dead adipocytes, which are dozens of micrometers in diameter. We describe a process, which we call digestive exophagy, in which macrophages create a tight seal in contact with the target, acidify the sealed zone and secrete lysosomal contents into the contact zone. By this process, hydrolysis by lysosomal enzymes occurs in a compartment that is outside the cell. We compare this process to the well characterized digestion of bone by osteoclasts, and we point out key similarities and differences.

exophagy phagocytosis lysosomes macrophages exocytosis


How do patients score cosmesis after laparoscopic natural orifice specimen extraction colectomy?

Abstract:
AIM
Laparoscopic colorectal resection results in improved cosmetic outcome and better presumed body image. Laparoscopic NOSE colectomy omits an incision for specimen extraction and is supposed to further improve postoperative cosmesis. This study aimed to assess the cosmetic benefit.

METHOD
Forty-nine patients who underwent a NOSE colectomy for bowel endometriosis from September 2009 to September 2013 were matched for age, American Society of Anesthesiologists (ASA) grade and body mass index (BMI) with patients who underwent a conventional laparoscopic colectomy for the same indication. Patients were asked to complete a questionnaire consisting of a body scale and a cosmetic scale and the Patient Scar Assessment Questionnaire (PSAQ) including five subscales (appearance, symptoms, scar consciousness, satisfaction with appearance and satisfaction with symptoms).

RESULTS
Patient demographics were similar between both groups. Patients were assessed at a median postoperative follow-up of 41 months in the NOSE colectomy group and 35 months in the conventional resection group. The median body image questionnaire score was 15 for NOSE colectomy and 18 for conventional resection (P = 0.027). The respective median PSAQ scores were 56 and 71 (P = 0.002). There was a good relationship between the PSAQ score and the body image questionnaire (Spearman correlation coefficient 0.82).

CONCLUSION
Depending on the scoring system used, the cosmetic outcome may be better after NOSE colectomy than conventional laparoscopy in patients having surgery for endometriosis. The comprehensive body image questionnaire, being shorter and easier to use, could be a valid tool for assessing cosmesis after NOSE procedures.

Wolthuis|A M|AM|
Meuleman|C|C|
Tomassetti|C|C|
D'Hooghe|T|T|
Fieuws|S|S|
de Buck van Overstraeten|A|A|
D'Hoore|A|A|

D057605:Natural Orifice Endoscopic Surgery

cosmesis
NOSE colectomy
endometriosis
Laparoscopy


Development of a finger adapter method for testing and evaluating vibration-reducing gloves and materials.

Abstract: The objective of this study was to develop a convenient and reliable adapter method for testing and evaluating vibration-reducing (VR) gloves and VR materials at the fingers. The general requirements and technical specifications for the design of the new adapter were based on our previous studies of hand-held adapters for vibration measurement and a conceptual model of the fingers-adapter-glove-handle system developed in this study. Two thicknesses (2 mm and 3 mm) of the adapter beam were fabricated using a 3-D printer. Each adapter is a thin beam equipped with a miniature tri-axial accelerometer (1.1 g) mounted at its center, with a total weight ≤ 2.2 g. To measure glove vibration transmissibility, the adapter is held with two gloved fingers; a finger is positioned on each side of the accelerometer. Each end of the adapter beam is slotted between the glove material and the finger. A series of experiments was conducted to evaluate this two-fingers-held adapter method by measuring the transmissibility of typical VR gloves and a sample VR material. The experimental results indicate that the major resonant frequency of the lightweight adapter on the VR material (≥800 Hz) is much higher than the resonant frequencies of the gloved fingers grasping a cylindrical handle (≤300 Hz). The experimental results were repeatable across the test treatments. The basic characteristics of the measured glove vibration transmissibility are consistent with the theoretical predictions based on the biodynamics of the gloved fingers-hand-arm system. The results suggest that VR glove fingers can effectively reduce only high-frequency vibration, and VR effectiveness can be increased by reducing the finger contact force. This study also demonstrated that the finger adapter method can be combined with the palm adapter method prescribed in the standardized glove test, which can double the test efficiency without substantially increasing the expense of the test.

Xu|Xueyan S|XS|
Welcome|Daniel E|DE|
Warren|Christopher M|CM|
McDowell|Thomas W|TW|
Dong|Ren G|RG|

Vibration-reducing glove
Anti-vibration glove
Glove finger test
Hand-arm vibration
Hand-transmitted vibration


Long-term home visiting with vulnerable young mothers: an interpretive description of the impact on public health nurses.

Abstract:
BACKGROUND
The Nurse-Family Partnership (NFP) is a targeted, nurse home visitation program for young, low-income, first-time mothers. While the effectiveness of the NFP has been established in the United States, and is currently being evaluated in the Canadian public health care system, we have minimal understanding of how work of this nature impacts public health nurses (PHNs), an essential component of this program delivery model, on both professional and personal levels.

METHODS
This two-phase study consisted of a qualitative secondary analysis of data from five focus groups conducted with PHNs (N = 6) who delivered the NFP intervention as part of a pilot study assessing feasibility and acceptability conducted in Hamilton, Ontario. The second phase, an interpretive description of individual interviews with the PHNs (N = 10) who have delivered the NFP in this context, further explored themes identified in the first phase. A practice, problem and needs analysis was conducted to describe and understand the phenomenon and promote sustainability of PHNs in this practice environment. Conventional content analysis was used to code and categorize data in the two datasets.

RESULTS
The nurse-client relationship, the core elements and structure of the NFP program and support of NFP colleagues were described as rewarding factors, while workload and workplace factors were identified as significant contributors to stress. PHNs described transforming their nursing practice through redefining success and shifting to a philosophy where the client is the expert of her own life. PHNs described the personal impact of worry about clients and doubt about their effectiveness in addressing client concerns. High levels of satisfaction were described in relation to the depth and intensity of relationships with clients and seeing them succeed over time.

CONCLUSIONS
PHNs are impacted in multiple ways by their work with vulnerable, young mothers. The study findings have implications for identification of strategies to support PHNs in reducing staff turnover, PHN burnout, secondary traumatic stress and compassion fatigue, and improving program delivery.

Dmytryshyn|Anne L|AL|
Jack|Susan M|SM|
Ballantyne|Marilyn|M|
Wahoush|Olive|O|
MacMillan|Harriet L|HL|

Home visiting
Public health nursing
Workplace factors
Burnout
Compassion fatigue
Compassion satisfaction


Synthesis and Evaluation of Cleistanthin A Derivatives as Potent Vacuolar H(+) -ATPase Inhibitors.

Abstract: Twelve new glycosides and alkane derivatives of cleistanthin A were designed and synthesized. Their in vitro antiproliferative activity was investigated against HCT-116, HepG2, A549, Hela tumor cell lines and HEK293 cell by MTT assay. Most of these compounds displayed antiproliferative effects on four cancer cells at submicromolar concentration, but they were less potent than cleistanthin A Moreover, they showed no antiproliferative effects on HEK293 cell at 200 nm. The most potent compounds, 3e and 4a, have been shown to inhibit the activity of vacuolar H(+) -ATPase (V-ATPase) and neutralize the pH of lysosomes at submicromolar concentrations.

Zhao|Yu|Y| Lu|Yapeng|Y| Ma|Jinlong|J| Zhu|Li|L|

D004354:Drug Screening Assays, Antitumor

synthesis
Cleistanthin A
inhibitor
vacuolar H+-ATPase


Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study.

Abstract:
BACKGROUND
The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians.

METHODS
Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0- to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing.

RESULTS
The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy.

CONCLUSIONS
Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population.

Suchy-Dicey|Astrid M|AM|
Shibata|Dean K|DK|
Madhyastha|Tara M|TM|
Grabowski|Thomas J|TJ|
Longstreth|W T|WT|
Buchwald|Dedra S|DS|

American Indians
MRI
Infarct
Hemorrhage
Central atrophy
Cerebral atrophy
White matter disease


Hexabromocyclododecane concentrations in Canadian human fetal liver and placental tissues.

Abstract: Detectable concentrations of the flame retardant hexabromocyclododecane (HBCD) have been reported in human tissues worldwide, but investigations to determine fetal exposure to this brominated flame retardant are lacking. This study was undertaken to determine the concentrations of α-, β- and γ-HBCD in human tissues (fetal liver and placenta) from Canada. Tissue samples were collected over a thirteen year period following elective pregnancy terminations in Montreal, Quebec, Canada. Samples were extracted using homogenisation with solvent, cleaned up using adsorption chromatography and analysis was performed with liquid chromatography-tandem mass spectrometry. Total HBCD concentrations ranged from below the limit of detection (<LOD; <1 ng g(-1)) to 4500 ng g(-1) lipid in fetal livers and <LOD (<1 ng g(-1)) to 5600 ng g(-1) lipid in placental tissue. No clear temporal trend was established in liver samples, nor was a significant relationship observed between fetal age and ΣHBCD concentrations. Temporal differences, however, were noted in placental tissues before and after 2005. HBCD concentrations in liver:placental paired tissue samples did not show a correlation. HBCD was found in placental tissues from Canadian women and results indicate that HBCD was present, at measurable concentrations, in developing fetuses from as early as 6.5 weeks.

Rawn|Dorothea F K|DF|
Gaertner|Dean W|DW|
Weber|Dorcas|D|
Curran|Ivan H A|IH|
Cooke|Gerard M|GM|
Goodyer|Cynthia G|CG|

Hexabromocyclododecane
HBCD
Human tissues
Brominated flame retardants
PBDEs


Long-term changes in blood pressure control in elementary school-aged children with sleep-disordered breathing.

Abstract:
OBJECTIVE
In adults sleep-disordered breathing (SDB) has been associated with impaired baroreflex control of blood pressure (BP), which has been linked to increased cardiovascular morbidity. In children, the long-term effects of SDB on baroreflex sensitivity (BRS) and BP variability (BPV) are unknown.

METHODS
Children previously diagnosed with SDB (n=40) and 20 nonsnoring controls aged 11-16 y underwent overnight polysomnography with continuous BP measurement, four years after the original diagnosis. At follow-up, SDB was categorized as resolved (absence of snoring and obstructive apnea hypopnea index (OAHI)≤1) or unresolved (continued to snore or had an OAHI>1). BRS and BPV were calculated using cross-spectral analysis and power spectral analysis, respectively.

RESULTS
Only children with resolved obstructive sleep apnea (OSA) at follow-up demonstrated an increase in BRS from 9.7±3 (ms mmHg(-1)) at baseline to 11.8±4 (ms mmHg(-1)) at follow-up (P=.03). However, children with all severities of both resolved and unresolved SDB showed a significant decrease in BPV from baseline to follow-up (a decrease in total power BPV (P<.05) and a shift in BPV spectra away from respiratory-related frequencies (increased low-frequency/high-frequency [LF/HF] ratio, P<.01). The change in OAHI was the sole determinant of change in BRS, HF power, and LF/HF ratio.

CONCLUSIONS
Improvement in SDB was associated with improved BP control, regardless if SDB was treated or spontaneously resolved four years after initial diagnosis. Our findings highlight the importance of monitoring children to ensure improvement of SDB and reduce the risk for cardiovascular morbidity in the future.

Vlahandonis|Anna|A|
Yiallourou|Stephanie R|SR|
Sands|Scott A|SA|
Nixon|Gillian M|GM|
Davey|Margot J|MJ|
Walter|Lisa M|LM|
Horne|Rosemary S C|RS|

Sleep-disordered breathing
Baroreflex sensitivity
Follow-up
Obstructive sleep apnea
Blood pressure variability
Pediatric


The Route of Motor Recovery in Stroke Patients Driven by Exoskeleton-Robot-Assisted Therapy: A Path-Analysis.

Abstract: Background: Exoskeleton-robot-assisted therapy is known to positively affect the recovery of arm functions in stroke patients. However, there is a lack of evidence regarding which variables might favor a better outcome and how this can be modulated by other factors. Methods: In this within-subject study, we evaluated the efficacy of a robot-assisted rehabilitation system in the recovery of upper limb functions. We performed a path analysis using a structural equation modeling approach in a large sample of 102 stroke patients (age 63.6 ± 13.1 years; 61% men) in the post-acute phase. They underwent 7 weeks of bilateral arm training assisted by an exoskeleton robot combined with a conventional treatment (consisting of simple physical activity together with occupational therapy). The upper extremity section of the Fugl-Meyer (FM-UE) scale at admission was used as a predictor of outcome, whereas age, gender, side of the lesion, days from the event, pain scale, duration of treatment, and number of sessions as mediators. Results: FM-UE at admission was a direct predictor of outcome, as measured by the motricity index of the contralateral upper limb and trunk control test, without any other mediating factors. Age, gender, days from the event, side of lesion, and pain scales were independently associated with outcomes. Conclusions: To the best of our knowledge, this is the first study assessing the relationship between clinical variables and outcomes induced by robot-assisted rehabilitation with a path-analysis model. We define a new route for motor recovery of stroke patients driven by exoskeleton-robot-assisted therapy, highlighting the role of FM-UE at admission as a useful predictor of outcome, although other variables need to be considered in the time-course of disease.

stroke
exoskeleton-robot-assisted therapy
path analysis
Fugl–Meyer


An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population.

Abstract:
BACKGROUND
Gamma-aminobutyric acid type A (GABAA) receptors mainly mediate the effects of gamma-aminobutyric acid, which is the primary inhibitory neurotransmitter in the central nervous system. Abundant evidence suggests that GABAA receptors play a key role in sleep-regulating processes. No genetic association study has explored the relationships between GABAA receptor genes and sleep duration, sleep quality, and sleep timing in humans.

METHODS
We determined the association between single-nucleotide polymorphisms (SNPs) in the GABAA receptor genes GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3 and sleep duration, sleep quality, and sleep timing in the Taiwan Biobank with a sample of 10,127 Taiwanese subjects. There were 10,142 subjects in the original study cohort. We excluded 15 subjects with a medication history of sedative-hypnotics.

RESULTS
Our data revealed an association of the GABRB3-GABRA5-GABRG3 gene cluster with sleep duration, which has not been previously identified: rs79333046 (beta = - 0.07; P = 1.21 × 10-3) in GABRB3, rs189790076 (beta = 0.92; P = 1.04 × 10-3) in GABRA5, and rs147619342 (beta = - 0.72; P = 3.97 × 10-3) in GABRG3. The association between rs189790076 in GABRA5 and sleep duration remained significant after Bonferroni correction. A variant (rs12438141) in GABRB3 was also found to act as a potential expression quantitative trait locus. Additionally, we discovered interactions between variants in the GABRB3-GABRA5-GABRG3 gene cluster and lifestyle factors, such as tea and coffee consumption, smoking, and physical activity, that influenced sleep duration, although some interactions became nonsignificant after Bonferroni correction. We also found interactions among GABRB3, GABRA5, and GABRG3 that affected sleep duration. Furthermore, we identified an association of rs7165524 (beta = - 0.06; P = 2.20 × 10-3) in GABRA5 with sleep quality and an association of rs79465949 (beta = - 0.12; P = 3.95 × 10-3) in GABRB3 with sleep timing, although these associations became nonsignificant after Bonferroni correction. However, we detected no evidence of an association of individual SNPs in GABRA1 and GABRA2.

CONCLUSIONS
Our results indicate that rs189790076 in GABRA5 and gene-gene interactions among GABRB3, GABRA5, and GABRG3 may contribute to sleep duration in the Taiwanese population.

Hou|Sheue-Jane|SJ|
Tsai|Shih-Jen|SJ|
Kuo|Po-Hsiu|PH|
Lin|Wan-Yu|WY|
Liu|Yu-Li|YL|
Yang|Albert C|AC|
Lin|Eugene|E|
Lan|Tsuo-Hung|TH|

Biobank
GABAA receptor gene
Sleep duration
GABRB3-GABRA5-GABRG3 gene cluster
Diverse populations
Gene–environment interaction
Gene–gene interaction


Correlation between blood glucose variability and the risk of death in patients with severe acute stroke.

Abstract: This study aimed to investigate the correlation between blood glucose variability and the risk of death in patients with severe acute stroke. One hundred and fifty-eight patients diagnosed with severe acute stroke were divided into survival group and death group and were retrospectively analyzed. The baseline National Institutes of Health Stroke Scale (NIHSS) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mean blood glucose, blood glucose standard deviation, mean amplitude of glycemic excursion, and mean variation coefficient of blood glucose were obtained and compared. Single-factor binary logistic regression analysis was used to determine the predictors of death in patients with severe acute stroke. The baseline NIHSS score (P<0.001), APACHE II score (P<0.001), blood glucose standard deviation (P<0.001), mean amplitude of glycemic excursion (P<0.001) and mean coefficient of variation of blood glucose (P<0.001), between the survival group and the death group significant difference. The results showed that baseline NIHSS score (OR, 1.08; 95% CI, 1.03 to 1.13, P=0.004), blood glucose standard deviation (OR, 1.14; 95% CI, 1.02 to 1.28, P=0.028), mean amplitude of glycemic excursion (OR, 1.38; 95% CI, 1.04 to 1.83, P=0.027), mean coefficient of variation of blood glucose (OR, 0.94; 95% CI, 0.73 to 1.21, P=0.03), are related to the death within 3 months in patients with severe acute stroke. The blood glucose variability is an independent predictor of death in patients with severe acute stroke. Great range of glycemic excursion indicates poor disease outcome. In contrast, the mean blood glucose level does not have significant correlation with the outcomes of patients.

Cai|Y|Y| Wang|C|C| Di|W|W| Li|W|W| Liu|J|J| Zhou|S|S|

Blood Glucose
Stroke
Brain Ischemia
Cerebral Hemorrhage
Critical Illness


First Evidence of a Protective Effect of Plant Bioactive Compounds against H2O2-Induced Aconitase Damage in Durum Wheat Mitochondria.

Abstract: In order to contribute to the understanding of the antioxidant behavior of plant bioactive compounds with respect to specific subcellular targets, in this study, their capability to protect aconitase activity from oxidative-mediated dysfunction was evaluated for the first time in plant mitochondria. Interest was focused on the Krebs cycle enzyme catalyzing the citrate/isocitrate interconversion via cis-aconitate, as it possesses a [4Fe-4S]2+ cluster at the active site, making it an early and highly sensitive target of reactive oxygen species (ROS)-induced oxidative damage. In particular, the effect on the aconitase reaction of five natural phenols, including ferulic acid, apigenin, quercetin, resveratrol, and curcumin, as well as of the isothiocyanate sulforaphane, was investigated in highly purified mitochondria obtained from durum wheat (DWM). Interestingly, a short-term (10 min) DWM pre-treatment with all investigated compounds, applied at 150 µM (75 µM in the case of resveratrol), completely prevented aconitase damage induced by a 15 min exposure of mitochondria to 500 µM H2O2. Curcumin and quercetin were also found to completely recover DWM-aconitase activity when phytochemical treatment was performed after H2O2 damage. In addition, all tested phytochemicals (except ferulic) induced a significant increase of aconitase activity in undamaged mitochondria. On the contrary, a relevant protective and recovery effect of only quercetin treatment was observed in terms of the aconitase activity of a commercial purified mammalian isoform, which was used for comparison. Overall, the results obtained in this study may suggest a possible role of phytochemicals in preserving plant mitochondrial aconitase activity, as well as energy metabolism, against oxidative damage that may occur under environmental stress conditions. Further investigations are needed to elucidate the physiological role and the mechanism responsible for this short-term protective effect.

aconitase
durum wheat
plant mitochondria
oxidative damage
phytochemicals
ROS
antioxidant capacity


Development of model for assessing the acceptance level of users in rural healthcare system of Tamilnadu, India.

Abstract:
BACKGROUND
HMIS will incorporate a paradigm shift in health such as removing manual records and transformation of data through the complex structure of health departments in Tamilnadu. Thus developing a model of technology acceptance in HMIS contest is important and necessary in order to promote usage of the HMIS in rural health care system.

OBJECTIVE
The papers purpose is to formulate a model of technology acceptance of Health Management Information System (HMIS) by generating and validating a research model that best describes rural health care workers usage behavior and behavior intention.

METHODS
This research proposes a theoretical framework which is comprised of key determinants that influence usage behavior of HMIS together with moderator. It has been tested through different parametric test and confirmatory factor analysis.

RESULTS
Data analysis shows that health workers innovativeness and voluntariness have a direct and positive influence on Technology Acceptance level and that the basic TAM hypotheses are fulfilled. HMIS usage behavior and behavior intention can be increased with factors that are effecting the successful implementation of HMIS when it remains high.

CONCLUSIONS
This research enables health departments to know which aspects of their HMIS components and variables to improve. This shows that HMIS usage and health workers/staffs acceptance level are key tools in the success of HMIS. This research has seemed to be done at the right time and in the right place to the best of its kind.

D001291:Attitude of Health Personnel
D001292:Attitude to Computers
D006282:Health Personnel
D006801:Humans
D007194:India
D008297:Male
D008331:Management Information Systems
D016134:Organizational Policy
D012041:Regional Medical Programs
D019035:Rural Health Services
D011795:Surveys and Questionnaires
D000078329:Workforce

health management information system
innovativeness
Voluntariness


The impact of extirpation of non-palpable/normal-sized regional lymph nodes on staging of canine cutaneous mast cell tumours: A multicentric retrospective study.

Abstract: Metastasis to regional lymph nodes (RLNs) in dogs with cutaneous mast cell tumour (cMCT) has been correlated with shortened survival time and higher risk of spread to distant sites. In the present study, extirpation of non-palpable or normal-sized RLNs was included in the surgical management of cMCT in dogs. Correlations between histological nodal status (HN0-3) and tumour variables were analysed. Ninety-three dogs with single cMCT without distant metastasis that underwent wide surgical excision of the primary tumour and extirpation of non-palpable or normal-sized RLN were included. The association between HN (HN0 vs HN > 0; HN0-1 vs HN2-3) and tumour variables (site, longest diameter, ulceration, 3-tier and 2-tier histological grades) was analysed by a generalized linear model with multinomial error. Then, 33 (35.5%) RLNs were HN0, 14 (15%) were HN1, 26 (28%) were HN2 and 20 (21.5%) were HN3. The presence of positive (HN > 0) RLN was significantly associated with cMCT larger than 3 cm. No other association was statistically significant. Non-palpable/normal-sized RLN in dogs with cMCT can harbour histologically detectable metastatic disease in nearly half of the cases. Extirpation of the RLN should always perfomed to obtain a correct staging of the disease, even in the absence of clinical suspicion of metastasis. Further studies should evaluate the possible therapeutical effect of the tumour burden reduction obtained by exrtipartion of a positive RLN.

dogs
lymph node excision
lymphatic metastasis
mastocytoma
neoplasm staging


Pestivirus control programs: how far have we come and where are we going?

Abstract: Classical swine fever (CSF) is endemic in large parts of the world and it is a major threat to the pig industry in general. Vaccination and stamping out have been the most successful tools for the control and elimination of the disease. The systematic use of modified live vaccines (MLV), which are very efficacious and safe, has often preceded the elimination of CSF from regions or countries. Oral vaccination using MLV is a powerful tool for the elimination of CSF from wild boar populations. Bovine virus diarrhea (BVD) is endemic in bovine populations worldwide and programs for its control are only slowly gaining ground. With two genotypes BVD virus (BVDV) is genetically more diverse than CSF virus (CSFV). BVDV crosses the placenta of pregnant cattle resulting in the birth of persistently infected (PI) calves. PI animals shed enormous amounts of virus for the rest of their lives and they are the reservoir for the spread of BVDV in cattle populations. They are the main reason for the failure of conventional control strategies based on vaccination only. In Europe two different approaches for the successful control of BVD are being used: Elimination of PI animals without or with the optional use of vaccines, respectively.

D001912:Bovine Virus Diarrhea-Mucosal Disease

pestivirus control
classical swine fever
bovine viral diarrhea


Job stress: Understanding the psychological risk factors of technocrat millennials from the socio-demographic perspective.

Abstract:
BACKGROUND
The Information Technology and Information Technology Enabled Services (IT and ITES) industry has been the backbone of the Indian economy. The sector is characterized by long working hours, strict deadlines, night shift, constant usage of computers, etc. Hence, the industry and nature of the job are influencing the psychological risk factors of the employees.

PURPOSE
The purpose of this paper is to explore the psychological risk factors (job stressors) of technocrat millennials and critically analyze them from the socio-demographic perspective.

METHODS
A single cross-sectional study with snowball sampling was collected from 300 technocrat millennials in Ahmedabad city (India). Job stressors are examined as psychological risk factors. MANOVA and independent-sample t-test has been put to use for establishing the relationship between psychological risk factors and socio-demographic variables.

RESULTS
The study highlighted that the experience, current position, size of family, number of children, gender, and family type had an impact on psychological risk factors of technocrat millennials.

CONCLUSIONS
The study contributes to the literature on the psychological risk factors and its association with demographic variables, and specifically in Ahmedabad city (India). Income did not have an impact on psychological risk factor; whereas education was the only demographic variable affecting the responsibility for persons. The experience influenced the role overload, role ambiguity, poor peer relations, and intrinsic impoverishment. The study explained each socio-demographic variable's impact on 12 psychological risk factors separately. The result of the paper will give insight to HR managers in the recruitment and selection of employees.

Information technology & information technology enabled services industry


Small-Molecule Dengue Virus Co-imprinting and Its Application as an Electrochemical Sensor.

Abstract: Polymers can be synthesized to recognize small molecules. This is achieved by introducing the target molecule during monomer self-assembly, where they can be incorporated during cross-linking polymerization. Following additional pre-processing, the material obtained can then be applied as a sensing layer for these molecules in many applications. The sensitivity of the polymers depends on the "active sites" imprinted on the surface. Increasing the number of active sites on the polymers surface can be achieved by using nanoparticles as a platform to support and concentrate the molecules for imprinting. In this work, we report the first use of dengue virus as a supporting nanoparticle to make for a more effective polymer composite sensor for the detection of bisphenol A (BPA), which is an environmental contaminant. The dengue virus has a nanoparticle size of around 100 nm and its surface provides regions where lipids and hydrophobic compounds can bind, making it an ideal support. The mixing of BPA with dengue prior to monomer self-assembly led to imprinted polymer surfaces with much higher density BPA binding sites and a limit of detection of 0.1 pm. We demonstrate that a BPA-dengue co-imprinting polymer composite sensor shows a very high sensitivity for BPA, but with lower production costs and technical requirements than other comparable methods.

Sukjee|Wannisa|W|
Tancharoen|Chompoonuch|C|
Yenchitsomanus|Pa-Thai|PT|
Gleeson|M Paul|MP|
Sangma|Chak|C|

dengue virus
self-assembly
bisphenol A
electrochemical sensing
molecularly imprinted polymers


A Reagentless Amperometric Formaldehyde-Selective Chemosensor Based on Platinized Gold Electrodes.

Abstract: Fabrication and characterization of a new amperometric chemosensor for accurate formaldehyde analysis based on platinized gold electrodes is described. The platinization process was performed electrochemically on the surface of 4 mm gold planar electrodes by both electrolysis and cyclic voltamperometry. The produced electrodes were characterized using scanning electron microscopy and X-ray spectral analysis. Using a low working potential (0.0 V vs. Ag/AgCl) enabled an essential increase in the chemosensor's selectivity for the target analyte. The sensitivity of the best chemosensor prototype to formaldehyde is uniquely high (28180 A·M-1·m-2) with a detection limit of 0.05 mM. The chemosensor remained stable over a one-year storage period. The formaldehye-selective chemosensor was tested on samples of commercial preparations. A high correlation was demonstrated between the results obtained by the proposed chemosensor, chemical and enzymatic methods (R = 0.998). The developed formaldehyde-selective amperometric chemosensor is very promising for use in industry and research, as well as for environmental control.

Demkiv|Olha|O| Smutok|Oleh|O| Gonchar|Mykhailo|M| Nisnevitch|Marina|M|

platinized gold electrode
amperometric chemosensor
formaldehyde


Biological effects of red beetroot and betalains: A review.

Abstract: Over the past few years, the use of natural substances as protective or therapeutic agents has gained much attention worldwide. Recent modern studies have shown a variety of health benefits for red beetroot and its active compounds betalains (also betanin) such as antioxidative, anti-inflammation, anticancer, blood pressure and lipid lowering, also antidiabetic and anti-obesity effects. Betanin, the main component of the red beetroot, is a betalain glycosidic pigment, which is used as a food additive. This review summarizes findings in the literature and shows the therapeutic potential of red beetroot and its active compounds (betalains) as promising alternatives for supplemental therapies in multiple diseases.

red beetroot
betalain
betanin
pharmacological effects


Transcriptional Control of Honey Bee (Apis mellifera) Major Royal Jelly Proteins by 20-Hydroxyecdysone.

Abstract: One of the first tasks of worker honey bees (Apis mellifera) during their lifetime is to feed the larval offspring. In brief, young workers (nurse bees) secrete a special food jelly that contains a large amount of unique major royal jelly proteins (MRJPs). The regulation of mrjp gene expression is not well understood, but the large upregulation in well-fed nurse bees suggests a tight repression until, or a massive induction upon, hatching of the adult worker bees. The lipoprotein vitellogenin, the synthesis of which is regulated by the two systemic hormones 20-hydroxyecdysone and juvenile hormone, is thought to be a precursor for the production of MRJPs. Thus, the regulation of mrjp expression by the said systemic hormones is likely. This study focusses on the role of 20-hydroxyecdysone by elucidating its effect on mrjp gene expression dynamics. Specifically, we tested whether 20-hydroxyecdysone displayed differential effects on various mrjps. We found that the expression of the mrjps (mrjp1⁻3) that were finally secreted in large amounts into the food jelly, in particular, were down regulated by 20-hydroxyecdysone treatment, with mrjp3 showing the highest repression value.

mrjp
vitellogenin
juvenile hormone
apalbumin
division of labor
ecdysone
social insect


Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

Abstract: Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations.

Hay|Colin W|CW|
Shanley|Lynne|L|
Davidson|Scott|S|
Cowie|Philip|P|
Lear|Marissa|M|
McGuffin|Peter|P|
Riedel|Gernot|G|
McEwan|Iain J|IJ|
MacKenzie|Alasdair|A|

Glucocorticoid receptor
TAC1 promoter
Gene regulation
Single nucleotide polymorphism
Stress and anxiety


Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2.

Abstract: Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors.

Guillon|Jean|J|
Le Borgne|Marc|M|
Rimbault|Charlotte|C|
Moreau|Stéphane|S|
Savrimoutou|Solène|S|
Pinaud|Noël|N|
Baratin|Sophie|S|
Marchivie|Mathieu|M|
Roche|Séverine|S|
Bollacke|Andre|A|
Pecci|Adali|A|
Alvarez|Lautaro|L|
Desplat|Vanessa|V|
Jose|Joachim|J|

Synthesis
Pyrrolo[1,2-a]quinoxaline
Protein kinase CK2
Antiproliferative activity


Assessing the Relation Between Flexibility in Emotional Expression and Symptoms of Anxiety and Depression: The Roles of Context Sensitivity and Feedback Sensitivity.

Abstract: Expressive flexibility (EF), the ability to enhance and suppress emotional expressions, predicts decreases in anxiety and depression symptoms years later (Bonanno, Papa, Lalande, Westphal, & Coifman, 2004). Bonanno and Burton (2013) proposed that knowing the most appropriate strategy for a situation (context sensitivity; CS), and awareness of how well strategies are working (feedback sensitivity; FS), partially explain this effect. We conducted a conditional process analysis to test this theory. One hundred thirty-eight undergraduates completed a behavioral measure of EF and self-reported symptoms of anxiety and depression, CS, and FS over one month. CS moderated the effect of EF on one-month changes in symptoms of anxiety and depression (p = .03): EF only predicted decreased anxiety and depression symptoms among people low in CS. FS mediated the effect of EF (95% CI: -.10, -.01) on changes in anxiety and depression symptoms: higher baseline EF was associated with higher two-week FS, which predicted decreased one-month anxiety and depression symptoms. Results suggest EF and CS may be compensatory skills and FS may be necessary to experience the adaptive effects of emotion regulation flexibility.

Southward|Matthew W|MW|
Cheavens|Jennifer S|JS|

flexibility
context
feedback sensitivity
emotion regulation
expressive regulation


Escape responses of fish: a review of the diversity in motor control, kinematics and behaviour.

Abstract: The study of fish escape responses has provided important insights into the accelerative motions and fast response times of these animals. In addition, the accessibility of the underlying neural circuits has made the escape response a fundamental model in neurobiology. Fish escape responses were originally viewed as highly stereotypic all-or-none behaviours. However, research on a wide variety of species has shown considerable taxon-specific and context-dependent variability in the kinematics and neural control of escape. In addition, escape-like motions have been reported: these resemble escape responses kinematically, but occur in situations that do not involve a response to a threatening stimulus. This Review focuses on the diversity of escape responses in fish by discussing recent work on: (1) the types of escape responses as defined by kinematic analysis (these include C- and S-starts, and single- versus double-bend responses); (2) the diversity of neuromuscular control; (3) the variability of escape responses in terms of behaviour and kinematics within the context of predator-prey interactions; and (4) the main escape-like motions observed in various species. Here, we aim to integrate recent knowledge on escape responses and highlight rich areas for research. Rapidly developing approaches for studying the kinematics of swimming motion both in the lab and within the natural environment provide new avenues for research on these critical and common behaviours.

Escape response
Fish
Kinematics
Swimming
Mauthner cells


Human-Wildlife Conflict: The Human Dimension of European Bison Conservation in the Bieszczady Mountains (Poland).

Abstract: An important limitation for the population growth of European bison in the Bieszczady Mountains may be the level of social acceptance. The study aimed to compare attitudes to European bison of local village inhabitants in Bieszczady and city dwellers in Rzeszów. We also investigated whether damage caused by European bison or other wild species changes peoples' perceptions of this animal. Our study showed that not only does the growing European bison population cause an increase in negative attitudes among local village communities, but this species also causes more conflict than any other herbivore in the Bieszczady Mountains. Village residents believed that the main threats that arise from European bison were the damage they cause and forest use limitations. The current compensation system for the damage caused by this species does not solve the problem because over 60% of damage is not effectively reported to the state administration. The city dwellers of Rzeszów displayed a different attitude towards the European bison. We concluded that while educational workshops for local villagers may alleviate conflict in the short-term, ultimately it is only by restricting the growth of the European bison population that a long-term effect will be achieved.

European bison
attitude
village
city
damage
forest
compensation
Carpathians
health risk
human–wildlife conflict


The degenerative lumbar disc: not a disease, but still an important consideration for OMPT practice: a review of the history and science of discogenic instability.

Abstract:
BACKGROUND
A recent AAOMPT position paper was published that opposed the use of the term 'degenerative disc disease' (DDD), in large part because it appears to be a common age-related finding. While common, there are significant physiologic and biomechanical changes that occur as a result of discogenic degeneration, which are relevant to consider during the practice of manual therapy.

METHODS
A narrative review provides an overview of these considerations, including a historical perspective of discogenic instability, the role of the disc as a pain generator, the basic science of a combined biomechanical and physiologic cycle of degeneration and subsequent discogenic instability, the influence of rotation on the degenerative segment, the implications of these factors for manual therapy practice, and a perspective on an evidence-based treatment approach to patients with concurrent low back pain and discogenic degeneration.

CONCLUSIONS
As we consider the role of imaging findings such as DDD, we pose the following question: Do our manual interventions reflect the scientifically proven biomechanical aspects of DDD, or have we chosen to ignore the helpful science as we discard the harmful diagnostic label?

review
Degenerative disc
physiology
biomechanics
low back pain
imaging
clinical reasoning
manipulation


Technology-based health solutions for cancer caregivers to better shoulder the impact of COVID-19: a systematic review protocol.

Abstract:
BACKGROUND
Cancer patients are particularly vulnerable to COVID-19, partially owing to their compromised immune systems and curbed or cut cancer healthcare services caused by the pandemic. As a result, cancer caregivers may have to shoulder triple crises: the COVID-19 pandemic, pronounced healthcare needs from the patient, and elevated need for care from within. While technology-based health interventions have the potential to address unique challenges cancer caregivers face amid COVID-19, limited insights are available. Thus, to bridge this gap, we aim to identify technology-based interventions designed for cancer caregivers and report the characteristics and effects of these interventions concerning cancer caregivers' distinctive challenges amid COVID-19.

METHODS
A systematic search of the literature will be conducted in PubMed, PsycINFO, CINAHL, and Scopus from the database inception to the end of March 2021. Articles that center on technology-based interventions for cancer caregivers will be included in the review. The search strategy will be developed in consultation with an academic librarian who is experienced in systematic review studies. Titles, abstracts, and full-text articles will be screened against eligibility criteria developed a priori. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedures will be followed for the reporting process.

CONCLUSIONS
COVID-19 has upended cancer care as we know it. Findings of this study can shed light on evidence-based and practical solutions cancer caregivers can utilize to mitigate the unique challenges they face amid COVID-19. Furthermore, results of this study will also offer valuable insights for researchers who aim to develop interventions for cancer caregivers in the context of COVID-19. In addition, we also expect to be able to identify areas for improvement that need to be addressed in order for health experts to more adequately help cancer caregivers weather the storm of global health crises like COVID-19 and beyond. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196301.

Su|Zhaohui|Z|0000-0003-2005-9504
McDonnell|Dean|D|
Liang|Bin|B|
Kue|Jennifer|J|
Li|Xiaoshan|X|
Šegalo|Sabina|S|
Advani|Shailesh|S|
Flores|Bertha E|BE|
Wang|Jing|J|

Cancer caregivers
COVID-19
Systematic review protocol
Cancer patients
Technology-based interventions
Coronavirus
Digital health solutions
Telemedicine


Pituitary volume in people with chronic schizophrenia: Clarifying the roles of serious violence and childhood maltreatment.

Abstract: Aberrations in stress-linked hypothalamic-pituitary-adrenal axis function have been independently associated with schizophrenia, antisocial behaviour and childhood maltreatment. In this study, we examined pituitary volume (PV) in relation to childhood maltreatment (physical abuse, sexual abuse, neglect) in men (i) with schizophrenia and a history of serious violence (n = 13), (ii) with schizophrenia but without a history of serious violence (n = 15), (iii) with antisocial personality disorder (ASPD) and a history of serious violence (n = 13), and (iv) healthy participants without a history of violence (n = 15). All participants underwent whole-brain magnetic resonance imaging. Experiences of childhood maltreatment were rated based on interviews (for all), and case history and clinical/forensic records (for patients only). There was a trend for smaller PV, on average, in schizophrenia patients (regardless of a history of violence), compared to the healthy group and the ASPD group; other group differences in PV were non-significant. Sexual abuse ratings correlated negatively with PVs in ASPD participants, but no significant association between childhood maltreatment and PV was found in schizophrenia participants. Our findings are consistent with previous evidence of smaller-than-normal PV in chronic schizophrenia patients, and suggest that illness-related influences may mask the possible sexual abuse-smaller PV association, seen here in ASPD, in this population.

Bipin|Minal|M|
Premkumar|Preethi|P|
Das|Mrigendra K|MK|
Lau|Jennifer Yf|JY|
Sumich|Alex L|AL|
Kumari|Veena|V|

Violence
Physical abuse
Sexual abuse
MRI
Stress


Enhanced RBC Aggregation in Type 2 Diabetes Patients.

Abstract:
BACKGROUND
This study aimed to investigate the relationship between HbA1c and RBC aggregation in type 2 diabetes mellitus (T2DM) patients by analysis of data from routine clinical tests and from in vitro experiments.

METHODS
A total of 2,111 inpatients with type 2 diabetes were selected and among them, 364 patients (Group A) had limited influence of plasma proteins on erythrocyte sedimentation rate (ESR) and was compared with the rest of the 1,747 inpatients (Group B). ESR, HbA1c , WBC, CRP, Fbg, and HCT were measured in all samples. Sixty samples were also collected from T2DM patients and used for in vitro ESR studies. Spearman's correlation coefficients were employed to reflect the correlation between ESR and other parameters. Mann-Whitney U test was used to compare the study parameters.

RESULTS
The test results for Group A were lower than Group B with respect to ESR, age, HCT, HbA1c , CRP, WBC, and Fbg. Only the difference in HbA1c , CRP, and Fbg values had statistical significance (P < 0.05). In addition, HbA1c correlated better with ESR for Group A (R = 0.622) than Group B (R = 0.563), whereas CRP and Fbg were contrary to this. In the in vitro studies, the HbA1c values were classified into the subgroups of 6.5-8.0%, 8.1-10%, and >10%. The corresponding ESR values were 28 ± 5.1 mm/h, 33 ± 2.7 mm/h, and 40 ± 4.1 mm/h, respectively.

CONCLUSION
ESR results of T2DM patients were elevated that was mainly caused by Fbg levels, and in addition HbA1c in part contributed to RBC aggregation.

D000328:Adult
D001799:Blood Sedimentation
D002097:C-Reactive Protein
D003924:Diabetes Mellitus, Type 2
D004903:Erythrocyte Aggregation
D006442:Glycated Hemoglobin A
D006801:Humans
D008875:Middle Aged
D012189:Retrospective Studies


Molecular Insights into the Enigmatic Metabolic Regulator, SnRK1.

Abstract: Sucrose non-fermenting-1 (SNF1)-related kinase 1 (SnRK1) lies at the heart of metabolic homeostasis in plants and is crucial for normal development and response to stress. Evolutionarily related to SNF1 in yeast and AMP-activated kinase (AMPK) in mammals, SnRK1 acts protectively to maintain homeostasis in the face of fluctuations in energy status. Despite a conserved function, the structure and regulation of the plant kinase differ considerably from its relatively well-understood opisthokont orthologues. In this review, we highlight the known plant-specific modes of regulation involving SnRK1 together with new insights based on a 3D molecular model of the kinase. We also summarise how these differences from other orthologues may be specific adaptations to plant metabolism, and offer insights into possible avenues of future inquiry into this enigmatic enzyme.

Emanuelle|Shane|S|
Doblin|Monika S|MS|
Stapleton|David I|DI|
Bacic|Antony|A|
Gooley|Paul R|PR|

D018506:Gene Expression Regulation, Plant

AMP-activated protein kinase (AMPK)
SNF1-related kinase 1 (SnRK1)
phosphorylation
plant metabolic control
sucrose non-fermenting 1 (SNF1)
trehalose-6-phosphate (T6P)


Genetic diversity of Gymnocypris chilianensis (Cypriniformes, Cyprinidae) unveiled by the mitochondrial DNA D-loop region.

Abstract: In order to analyze the genetic diversity and genetic differentiation of Gymnocypris chilianensis, D-loop region of the mitochondrial DNA was sequenced in 50 individuals of G. chilianensis obtained from 2 geographic locations (Heihe River and Shule River) and 25 individuals of G. przewalskii (Qinghai Lake). Twenty-five homologous sequences of another G. eckloni (Yellow River) downloaded from GenBank were analyzed together. The sequences were analyzed by using the MEGA (version 7.0) and DnaSP (version 6.0) software. The results revealed that 82 haplotypes were detected among 100 individuals. The haplotype diversity (Hd) and nucleotide diversity (Pi) of G. chilianensis of the Shule River were 0.963 ± 0.029 and 0.00414 ± 0.00069, which were lower than those of 3 other populations. The genetic distance of G. chilianensis in both Heihe River and Shule River was 0.0013. The genetic distances between the 2 G. chilianensis populations and the G. eckloni were 0.0148 and 0.0141, respectively. Population differentiation values (Fst) and gene flow (Nm) showed that 4 population had occurred obvious genetic differentiation (Fst: 0.20811 ∼ 0.98863. p < 0.01; Nm < 1). Compared with G. przewalskii and G. eckloni, the differentiation degree was more significant between Heihe River G. chilianensis and Shule River G. chilianensis (Fst = 0.98863, p < 0.01; Nm = 0.00287). Maximum Likelihood (ML) phylogenetic tree showed that G. chilianensis had further genetic distance with G. eckloni and G. przewalskii. In conclution, G. chilianensis (HH&SL) had lower genetic diversity and further genetic distance than G. przewalskii (QH) and G. eckloni (YL). We suggest strengthen the protection of genetic resources of G. chilianensis.

genetic diversity
Gymnocypris chilianensis
D-loop
genetic differentiation


The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use.

Abstract: The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols. In this context, the cocaine derivative (E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4'-tolyl)nortropane, or LBT-999, has passed all the required stages of the development that makes it now a highly relevant imaging tool, particularly in the context of Parkinson's disease. This review describes the different steps of the development of LBT-999 which initially came from its non-fluorinated derivative (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3-(4-methylphenyl) nortropane, or PE2I, because of its high promising properties. [18F]LBT-999 has been extensively characterized in rodent and non-human primate models, in which it demonstrated its capability to explore in vivo the DAT localized at the dopaminergic nerve endings as well as at the mesencephalic cell bodies, in physiological conditions. In lesion-induced rat models of Parkinson's disease, [18F]LBT-999 was able to precisely quantify in vivo the dopaminergic neuron loss, and to assess the beneficial effects of therapeutic approaches such as pharmacological treatment and cell transplantation. Finally recent clinical data demonstrated the efficiency of [18F]LBT-999 in the diagnosis of Parkinson's disease.

Chalon|Sylvie|S|
Vercouillie|Johnny|J|
Payoux|Pierre|P|
Deloye|Jean-Bernard|JB|
Malherbe|Cécile|C|
Le Jeune|Florence|F|
Arlicot|Nicolas|N|
Salabert|Anne-Sophie|AS|
Guilloteau|Denis|D|
Emond|Patrick|P|
Ribeiro|Maria-Joao|MJ|

PET
radiopharmaceutical
Parkinson's disease
dopaminergic neuron
basal ganglia


A cost-effective approach to factor assay calibration using a truncated live calibration curve.

Abstract:
INTRODUCTION
The measurements of clotting factor activities are usually performed using a one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). Advances in automated coagulation analysers have led to the utilization of stored calibration curves. There are sometimes substantial intervals between test calibration and analysis of samples. Variability in results can be influenced by calibrant and methodology. Several guidelines recommend calibration and patient samples be performed together in parallel; this incurs costs, but reliance on a stored calibration curve may lead to inaccuracy of results over time.

METHODS
We evaluated inclusion of a live truncated (3 point) calibration curve using calibrator plasma alongside test samples and compared results calculated against the stored calibration curves and live truncated calibration to assess the impact on precision and accuracy. The feasibility of this was tested on two hospital sites in the UK; OSA and CSA were performed on Sysmex CS5100 using Actin FS, SynthASil, Innovin, Biophen chromogenic VIII and Rossix chromogenic IX.

RESULTS
Results of two batches of IQC were compared for FII, FV, FVII, FX, FIX:C, FXI, FXII and OSA FVIII (FVIII:C1) and CSA FVIII:C (FVIII:CR) and FXI:C. By utilizing a live truncated calibration, precision improved with the most striking examples: FXII %CV 23.1% to 3.1% (site A) FXI 7.3% to 2.4% (site B). The improvement in other clotting factors was more modest.

CONCLUSION
To the best of our knowledge, this is the first study that demonstrates that the use of a live truncated calibration curve will improve precision and accuracy.

D001777:Blood Coagulation
D001779:Blood Coagulation Factors
D001780:Blood Coagulation Tests
D002138:Calibration
D002863:Chromogenic Compounds
D003362:Cost-Benefit Analysis
D005169:Factor VIII
D006801:Humans
D011994:Recombinant Proteins
D012015:Reference Standards
D015203:Reproducibility of Results
D013925:Thromboplastin

factor assay
calibration
APTT
PT
cost effective


Expression, purification, crystallization and structure determination of the N terminal domain of Fhb, a factor H binding protein from Streptococcus suis.

Abstract: Fhb is a surface virulence protein from Streptococcus suis, which could aid bacterial evasion of host innate immune defense by recruiting complement regulator factor H to inactivate C3b deposited on bacterial surface in blood. Here we successfully expressed and purified the N terminal domain of Fhb (N-Fhb) and obtained crystals of the N-Fhb by sitting-drop vapor diffusion method with a resolution of 1.50 Å. The crystals belong to space group C2 with unit cell parameters a = 127.1 Å, b = 77.3 Å, c = 131.6 Å, α = 90°, β = 115.9°, γ = 90°. The structure of N-Fhb was determined by SAD method and the core structure of N-Fhb is a β sandwich. We speculated that binding of Fhb to human factor H may be mainly mediated by surface amino acids with negative charges.

Zhang|Chunmao|C| Yu|You|Y| Yang|Maojun|M| Jiang|Yongqiang|Y|

D000818:Animals
D001426:Bacterial Proteins
D002352:Carrier Proteins
D017242:Complement Factor H
D003460:Crystallization
D018360:Crystallography, X-Ray
D006801:Humans
D057131:Immune Evasion
D007113:Immunity, Innate
D008958:Models, Molecular
D017434:Protein Structure, Tertiary
D011994:Recombinant Proteins
D055672:Static Electricity
D017011:Streptococcus suis
D014774:Virulence

Fhb
Streptococcus suis
β sandwich
Negative charges
Crystal structure


Deletion of p21/Cdkn1a confers protective effect against prostate tumorigenesis in transgenic adenocarcinoma of the mouse prostate model.

Abstract: Cyclin-dependent kinase inhibitors (CDKIs) p21(Cip1/Waf1) (p21) and p27(Kip1) (p27) play a determining role in cell cycle progression by regulating CDK activity; however, p21 role in prostate cancer (PCa) is controversial. Whereas p21 upregulation by anticancer agents causes cell cycle arrest in various PCa cell lines, elevated p21 levels have been associated with higher Gleason score, poor survival and increased PCa recurrence. These conflicting findings suggest that more studies are needed to examine p21 role in PCa. Herein, employing genetic approach, transgenic mice harboring p21/Cdkn1a homozygous deletion (p21(-/-)) were crossed with the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice to characterize in vivo consequences of p21 deletion on prostate tumorigenesis. Lower urogenital tract weight of p21(-/-)/TRAMP mice was significantly lower than those of p21(+/-)/TRAMP and TRAMP mice. Histopathology further supported these observations, showing less aggressiveness in prostates of p21(-/-)/TRAMP. Furthermore, a significantly higher incidence of low-grade prostatic intraepithelial lesions (PIN) with a concomitant reduction in adenocarcinoma incidence was observed in p21(-/-)/TRAMP mice compared with TRAMP mice. In addition, whereas TRAMP mice showed the presence of poorly differentiated adenocarcinoma lesions, no such lesions were observed in p21/TRAMP transgenic mice. Specifically, there was a significant reduction in the severity of lesions in both p21(-/-)/TRAMP and p21(+/-)/TRAMP mice compared with TRAMP mice. Together, our data showed that p21 deletion reduces prostate tumorigenesis by slowing-down progression of PIN (pre-malignant) to adenocarcinoma (malignant), suggesting that intact p21 expression is associated with PCa aggressiveness, while its decreased levels may in fact confer protection against prostate tumorigenesis.

Jain|Anil K|AK|
Raina|Komal|K|
Agarwal|Rajesh|R|

D050759:Cyclin-Dependent Kinase Inhibitor p21

cell cycle
prostate cancer
TRAMP
p21 knockdown


Preliminary Investigation of Species Diversity of Rice Hopper Parasitoids in Southeast Asia.

Abstract: Ongoing intensification of rice production systems in Southeast Asia is causing devastating yield losses each year due to rice hoppers. Their continuing development of immunity to resistant rice varieties and pesticide applications further complicates this problem. Hence, there is a high demand for biological control agents of rice hoppers. Egg parasitoid wasps are among the most important natural enemies of rice hoppers, such as Nilaparvata lugens and Nephotettix spp. However, our knowledge of their diversity is still very limited, due to their small size and the lack of available morphological information. Classifying these parasitoids is the first step to properly understanding their role in the rice agroecosystem. We used traditional morphological identification, as well as DNA sequencing of the 28S rRNA and the COI genes, to investigate the diversity of four important hopper egg parasitoid genera in the Philippines. Parasitoids of the genera Anagrus, Oligosita, Gonatocerus, and Paracentrobia were collected in eight study landscapes located in Luzon. Our findings illustrate that characterization of species diversity using morphological and molecular analyses were concordant only for the genus Paracentrobia. The genera Anagrus and Gonatocerus exhibited more genetic diversity than estimated with the morphological analysis, while the opposite was observed for Oligosita. This is the first study investigating the molecular diversity of rice hopper parasitoids in the Philippines. More research combining morphological, behavioral, and molecular methods, as well as the establishment of a comprehensive DNA database, are urgently needed to assess the performance and suitability of these organisms as biocontrol agents.

rice
Nilaparvata lugens
Nephotettix
genetic diversity
DNA barcoding
hymenopteran parasitoids


Socio-demographic, Behavioral and Health Characteristics of Underage Female Sex Workers in Mozambique: The Need to Protect a Generation from HIV Risk.

Abstract: Characteristics, HIV risk, and program coverage for underage female sex workers (FSW) are rarely systematically described worldwide. We compared characteristics of underage (15-17 years old) and adult (≥18 years old) FSW in three main urban areas of Mozambique (Maputo, Beira and Nampula) using data from three respondent-driven sampling surveys implemented in 2011-2012. Among survey participants, 9.8 % (39/400) in Maputo, 17.0 % (70/411) in Beira and 25.6 % (110/429) in Nampula were underage. Over half reported performing sex work to afford daily living, and 29.7-50.0 % had unprotected sex with their last client. The proportion of underage FSW having accessed care and prevention services was lower compared to adult FSW. While HIV prevalence among underage FSW was lower than in adults, it increased markedly with age. Our results point to the urgency of expanding prevention and care programs geared towards underage FSW.

Inguane|Celso|C|
Horth|Roberta Z|RZ|
Miranda|Angélica E|AE|
Young|Peter W|PW|
Sathane|Isabel|I|
Cummings|Beverley E|BE|
Augusto|Ângelo|Â|
Raymond|Henry F|HF|
Mcfarland|Willi|W|


Probiotics and immunity: provisional role for personalized diets and disease prevention.

Abstract: There is great interest in the interaction between diet and immune system and concomitantly in the potential of probiotic bacteria, especially given recent advances in understanding of gut microbiota effects on health in the context of microbiome research. Following our recent study on bacterial wall elasticity as a predictive measure of phagocytic cellular reactions and related outcomes, a question was raised regarding the scope of the application of these findings in various medical conditions in the context of predictive, preventive, and personalized medicine (PPPM). This summarizing review of the data describes the contributions, both observed and potential, of probiotics to the gut-brain axis and various medical conditions, including immune and atopic states, metabolic and inflammatory diseases-including liver disease and diabetes mellitus-cancer, and more. It also suggests novel insights for a number of beneficial applications of probiotics and advances in development of novel probiotic-based treatments and personalized diets, as well as application of sophisticated imaging techniques and nanobiotechnologies that can be adopted in the near future by innovative medical experts, warranting further research and practical translation.

Bubnov|Rostyslav V|RV|
Spivak|Mykola Ya|MY|
Lazarenko|Liudmyla M|LM|
Bomba|Alojz|A|
Boyko|Nadiya V|NV|

Preventive
Gut microbiota
Microbiome
Predictive
and personalized medicine
Gut-brain axis
Bifidobacterium
Cancer
Dietary biomarkers
Fecal microbiota transplantation
Healthy diet
Immune disorders
Lactobacillus
Nutrition
Pattern recognition receptors


Lithium and Tamoxifen Modulate Behavior and Protein Kinase C Activity in the Animal Model of Mania Induced by Ouabain.

Abstract:
Background
The intracerebroventricular injection of ouabain, a specific inhibitor of the Na+/K+-adenosine-triphosphatase (Na+/K+-ATPase) enzyme, induces hyperactivity in rats in a putative animal model of mania. Several evidences have suggested that the protein kinase C signaling pathway is involved in bipolar disorder. In addition, it is known that protein kinase C inhibitors, such as lithium and tamoxifen, are effective in treating acute mania.

Methods
In the present study, we investigated the effects of lithium and tamoxifen on the protein kinase C signaling pathway in the frontal cortex and hippocampus of rats submitted to the animal model of mania induced by ouabain. We showed that ouabain induced hyperlocomotion in the rats.

Results
Ouabain increased the protein kinase C activity and the protein kinase C and MARCKS phosphorylation in frontal cortex and hippocampus of rats. Lithium and tamoxifen reversed the behavioral and protein kinase C pathway changes induced by ouabain. These findings indicate that the Na+/K+-ATPase inhibition can lead to protein kinase C alteration.

Conclusions
The present study showed that lithium and tamoxifen modulate changes in the behavior and protein kinase C signalling pathway alterations induced by ouabain, underlining the need for more studies of protein kinase C as a possible target for treatment of bipolar disorder.

Valvassori|Samira S|SS|
Dal-Pont|Gustavo C|GC|
Resende|Wilson R|WR|
Varela|Roger B|RB|
Peterle|Bruna R|BR|
Gava|Fernanda F|FF|
Mina|Francielle G|FG|
Cararo|José H|JH|
Carvalho|André F|AF|
Quevedo|João|J|

protein kinase C
animal model of mania
ouabain
Na+/K+-ATPase
bipolar disorder


CMUT-based biosensor with convolutional neural network signal processing.

Abstract: The improvement of the micromachined ultrasound transducer based (CMUT) biosensor fabrication technology and signal processing, which led to higher signal to noise ratio is reported. The biosensor contains interdigitally arranged CMUT structure with gold-coated analytical area. It is assembled with the plexiglass microchannels. CMUTs were fabricated with the wafer bonding technology for 5 MHz operation in immersion. For signal processing the convolutional neural network (CNN) was developed and trained to classify the sensor data to different propagation delay values. For training of the network 750 thousand signals representing different properties of the bioanalyte and different noise conditions was simulated by the finite time difference domain (FDTD) model. The capability of the CNN algorithm to classify the propagation delay data was compared with the adaptive passband filter signal processing algorithm used in our previous version of the senor. Both sensing channels were run simultaneously with the reference liquids in the microchannel: deionized water switching to 0.9% saline. It was found that CNN channel is capable to improve the signal to noise ratio for this experiment to 75 dB, when the same property for the passband filter channel was only 60 dB. This led to the generalization about the advantage of CNN channel to provide 15 dB less of instrumental noise. Finally, the real-time detection ability of the bovine serum albumin (BSA) deposition on the analytical area of improved sensor was demonstrated.

Pelenis|Donatas|D| Barauskas|Dovydas|D| Vanagas|Gailius|G| Dzikaras|Mindaugas|M| Viržonis|Darius|D|


Breast volume estimation from systematic series of CT scans using the Cavalieri principle and 3D reconstruction.

Abstract:
OBJECTIVES
Preoperative breast volume estimation is very important for the success of the breast surgery. In the present study, two different breast volume determination methods, Cavalieri principle and 3D reconstruction were compared.

MATERIAL AND METHODS
Consecutive sections were taken in slice thickness of 5 mm. Every 2nd breast section in a set of consecutive sections was selected. We marked breast tissue with blue line on each selected section, and so prepared CT scans used for breast volume estimation. The volumes of the 60 breasts were estimated using the Cavalieri principle and 3D reconstruction.

RESULTS
The mean breast volume value was established to be 467.79 ± 188.90 cm(3) with Cavalieri method and 465.91 ± 191.41 cm(3) with 3D reconstruction. The mean CE for the estimates in this study was calculated as 0.25%. Skin-sparing volume was about 91.64% of the whole breast volume. Both methods are very accurate and have a strong linear association.

CONCLUSION
Our results suggest that the calculation of breast volume or its part in vivo from systematic series of CT scans using the Cavalieri principle or 3D breast reconstruction is accurate enough to have a significant clinical benefit in planning reconstructive breast surgery. These methods can help the surgeon guide the choice of the most appropriate implant or/and flap preoperatively.

Erić|Mirela|M| Anderla|Andraš|A| Stefanović|Darko|D| Drapšin|Miodrag|M|

Breast
Volume estimation
Cavalieri principle
3D reconstruction
CAD software
SolidWorks


Analysis of the greater palatine foramen in a Lebanese population using cone-beam computed tomography technology.

Abstract:
OBJECTIVE
The aim of this study was to describe the diameter and the position of the greater palatine foramen (GPF) in relation to adjacent anatomical landmarks in the maxilla in a Lebanese population using cone-beam computed tomography (CBCT) technology.

MATERIALS AND METHODS
CBCT images of 58 Lebanese adult patients were included in this study and a total of 116 GPF were evaluated bilaterally. The diameter of the GPF and its position relative to the maxillary molars, and distances to the midline maxillary suture and to the anterior nasal spine were analyzed.

RESULTS
Of all foramina assessed, 41.38% were located opposite to the third molar, 29.31% were distal to it, 27.59% were between the second and the third, and only 1.72% were opposite to the second. The average diameter was 5.633 mm on the right and 5.723 mm on the left, and the average distances to midline maxillary suture and anterior nasal spine were 16.228 mm and 48.294 mm on the right and 14.907 mm and 48.122 mm on the left, respectively.

CONCLUSION
Within the limits of this study, we conclude that in Lebanese patients, the GPF location is variable, very rarely opposite to the second molar, and more closely related to the third, but may present mesial or distal to it in one-fourth of patients.

Aoun|Georges|G| Nasseh|Ibrahim|I| Sokhn|Sayde|S| Saadeh|Maria|M|

greater palatine foramen
Lebanese population
Cone-beam computed tomography


LC-MS-Based Metabolomics of Biofluids Using All-Ion Fragmentation (AIF) Acquisition.

Abstract: The field of liquid chromatography-mass spectrometry (LC-MS)-based nontargeted metabolomics has advanced significantly and can provide information on thousands of compounds in biological samples. However, compound identification remains a major challenge, which is crucial in interpreting the biological function of metabolites. Herein, we present a LC-MS method using the all-ion fragmentation (AIF) approach in combination with a data processing method using an in-house spectral library. For the purposes of increasing accuracy in metabolite annotation, up to four criteria are used: (1) accurate mass, (2) retention time, (3) MS/MS fragments, and (4) product/precursor ion ratios. The relative standard deviation between ion ratios of a metabolite in a biofluid vs. its analytical standard is used as an additional metric for confirming metabolite identity. Furthermore, we include a scheme to distinguish co-eluting isobaric compounds. Our method enables database-dependent targeted as well as nontargeted metabolomics analysis from the same data acquisition, while simultaneously improving the accuracy in metabolite identification to increase the quality of the resulting biological information.

Chaleckis|Romanas|R|
Naz|Shama|S|
Meister|Isabel|I|
Wheelock|Craig E|CE|

Liquid chromatography-mass spectrometry (LC-MS)


Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium.

Abstract: The mammalian intestine is colonized by trillions of bacteria that perform essential metabolic functions for their hosts. The mutualistic nature of this relationship depends on maintaining spatial segregation between these bacteria and the intestinal epithelial surface. This segregation is achieved in part by the presence of a dense mucus layer at the epithelial surface and by the production of antimicrobial proteins that are secreted by epithelial cells into the mucus layer. Here, we show that resistin-like molecule β (RELMβ) is a bactericidal protein that limits contact between Gram-negative bacteria and the colonic epithelial surface. Mouse and human RELMβ selectively killed Gram-negative bacteria by forming size-selective pores that permeabilized bacterial membranes. In mice lacking RELMβ, Proteobacteria were present in the inner mucus layer and invaded mucosal tissues. Another RELM family member, human resistin, was also bactericidal, suggesting that bactericidal activity is a conserved function of the RELM family. Our findings thus identify the RELM family as a unique family of bactericidal proteins and show that RELMβ promotes host-bacterial mutualism by regulating the spatial segregation between the microbiota and the intestinal epithelium.

Propheter|Daniel C|DC|
Chara|Andrew L|AL|
Harris|Tamia A|TA|
Ruhn|Kelly A|KA|
Hooper|Lora V|LV|0000-0002-2759-4641

D036341:Intercellular Signaling Peptides and Proteins

microbiota
intestinal epithelium
antibacterial protein
innate immunity


Multimodal prediction of dementia with up to 10 years follow up: the Gothenburg MCI study.

Abstract:
BACKGROUND
Neuropsychological tests, CSF Aβ42, T-tau, P-tau181, hippocampal volume, and white matter lesions have been shown to predict conversion to dementia in patients with mild cognitive impairment (MCI).

OBJECTIVE
To examine the predictive value of combinations of these markers and to examine if the absence of pathological markers provides a lasting reduction of conversion rates.

METHODS
The Gothenburg MCI study is a clinically based study. Seventy-three MCI patients were included in the present sub-study and followed for a maximum of ten years. Thirty-four patients converted to dementia (18 to AD) and 39 remained stable. At inclusion, patients were classified into positive or negative risk groups according to results from neuropsychological testing (Rey auditory verbal learning test, Boston naming test, Trail making test B), CSF biomarkers (amyloid β42, T-tau, and P-tau181), and MRI scans (hippocampal volume, white matter lesions).

RESULTS
Trail making test B (TMT-B) was the best single predictor for the prediction of dementia (AUC 0.89, HR 25), and T-tau was the best predictor of AD (AUC 0.97, HR 41). The combination of hippocampal volume and TMT-B was the best combination for the prediction of dementia (HR 25), and the combination of hippocampal volume and T-tau was the best combination for the prediction of AD (HR 37).

CONCLUSION
Neuropsychological tests, CSF markers, and hippocampal volume predicted conversion from MCI to AD and general dementia. The absence of pathological markers provided a long-time protection from dementia.

Eckerström|Carl|C| Olsson|Erik|E| Klasson|Niklas|N| Berge|Josef|J| Nordlund|Arto|A| Bjerke|Maria|M| Wallin|Anders|A|

D000368:Aged
D000544:Alzheimer Disease
D016229:Amyloid beta-Peptides
D019540:Area Under Curve
D060825:Cognitive Dysfunction
D003704:Dementia
D018450:Disease Progression
D005260:Female
D006624:Hippocampus
D006801:Humans
D008137:Longitudinal Studies
D008279:Magnetic Resonance Imaging
D008297:Male
D008609:Mental Status Schedule
D008875:Middle Aged
D009483:Neuropsychological Tests
D011237:Predictive Value of Tests
D016875:tau Proteins

dementia
neuropsychological test
mild cognitive impairment
Cerebrospinal fluid
magnetic resonance imaging


Swine used in the medical university: overview of 20 years of experience.

Abstract: Center for Development of Advanced Medical Technology (CDAMTec) in Jichi Medical University was established in 2009. It is the first educational research facility specialized for medical research and training using swine in Japan. Preclinical studies on large animals are essential prior to clinical trials to develop regenerative medical products and medical equipment. We have continued comprehensively considering using miniature swine for experiments to develop advanced medical technologies and train physicians with advanced clinical abilities, while paying attention to animal welfare. The center plays a pioneering role in this field by accumulating know-how such as (1) Construction and effective utilization of research facilities, (2) Procurement of quality animal resources, (3) Education and training of technical staff, (4) Establishment of support system for physicians and researchers. We now open up widely these expertise and foundation for medical research and training not only within our university but also outside the university, so as to move faster to practical use of advanced medical technology and contribute to human health and welfare.

D005160:Facility Design and Construction

swine
facility
animal welfare
management
preclinical model


Occurrence and emission of phthalates, bisphenol A, and oestrogenic compounds in concentrated animal feeding operations in Southern China.

Abstract: Phthalates (PAEs), bisphenol A (BPA), and oestrogenic compounds have become major concerns due to their endocrine-disrupting effect. However, few studies related to the occurrence of PAEs, BPA, and oestrogen in food and compost from different growth age livestock have been conducted. In this study, faeces, urine and food samples were collected from a typical livestock (cow) and a special livestock (pigeon) from concentrated animal feeding operations (CAFOs). The daily total oestrogen excretion of a single cow ranged from 192 μg/day to 671 μg/day, which was significantly higher than that of a single pigeon (0-0.01 μg/day). Conjugated oestrogens represented 22.0-46.0% of the total oestrogens excreted from cow faeces and 80.7-91.8% of those from cow urine, indicating that the form of the excreted oestrogens depends on the livestock species and type of excrement. BPA was all detected in all livestock manure and food, and the concentration in pigeon was 9.2-40.2 ng/g and 23.1 ng/g respectively, while that in cattle was 50.5-72.0 ng/g and 41.1 ng/g respectively. The results indicated that the food is significant sources of BPA entering the process of cow and pigeon breeding. Diethyl phthalate (DEP) was detected at high frequency in pigeon faeces samples, suggesting that pigeons were highly exposed to these plasticisers. The total oestradiol equivalent quantity (EEQt) of livestock origin in aquatic environments was estimated to be 2.99 ng/L, which was higher than the baseline hazard value (1 ng/L) (Xu et al., 2018). The study provides data on the emissions and sources of PAEs, BPA, and oestrogenic compounds from different livestock in CAFOs and demonstrates that food is a significant source of BPA entering livestock.

Tao|Huan-Yu|HY| Zhang|Jiawei|J| Shi|Jianghong|J| Guo|Wei|W| Liu|Xiaowei|X| Zhang|Mengtao|M| Ge|Hui|H| Li|Xiao-Yan|XY|

Phthalates Oestrogen BPA Livestock CAFOs


Swallowing Outcomes in 7 Patients Following Endoscopic Cricopharyngeal Myotomy With Primary Closure.

Abstract: Cricopharyngeal spasm and pharyngeal pouch can result in severe dysphagia symptoms that can have a significant impact on a patient's quality of life. Several surgical interventions have been demonstrated including balloon dilatation, botox injection, and open and endoscopic cricopharyngeal myotomy. The aim of this case series is to describe our technique for endoscopic cricopharyngeal myotomy and compare pre- and postoperative swallowing outcomes using objective swallowing questionnaires in a small series of patients. Seven patients diagnosed with cricopharyngeal spasm or grade 1 pharyngeal pouch on barium swallow were prospectively observed. MD Anderson Dysphagia inventory (MDADI) and Dysphagia handicap index (DHI) were given to patients before and after their operation. All patients underwent the same surgical technique with the cricopharyngeal bar divided and the defect closed with dissolvable sutures. Mean inpatient stay was 7 days (range 1-8) and mean time to resumption of soft diet was 4 (range 1-7) days. All patients resumed oral diet before discharge. MDADI scores showed improvement across all domains, however only the emotional score achieved statistical significance (P = .04). Dysphagia handicap index scores showed a statistically significant improvement across functional, emotional, and total domains. Postoperative chest infection treated with oral antibiotics occurred in 3 patients (43%) and no other complications were documented. In conclusion, endoscopic cricopharyngeal myotomy with primary sutured endoscopic closure can result in a significant benefit to patient's swallowing symptoms, emotional well-being, and quality of life.

Zenker diverticulum
deglutination disorders
esophogeal motility disorder
pharyngeal muscles


Electrochemiluminescence (ECL) immunosensor for detection of Francisella tularensis on screen-printed gold electrode array.

Abstract: An electrochemiluminescence (ECL) immunosensor for the rapid detection of the Francisella tularensis pathogen using whole antibodies or antibody fragments as capture biomolecule is described. A sandwich immunoassay was used with either lipopolysaccharide (LPS) or the whole inactivated bacterial cell (LVS) as a target, while Ru(bpy)3 (2+)-encapsulated silicate nanoparticles were linked to the secondary antibody and used as ECL labels. The assay was performed in a fluidic chip housed in a custom-built black box incorporating electronics, optics and fluidics. The obtained limit of detection for LPS was 0.4 ng/mL, while for the LVS it was 70 and 45 bacteria/mL when the capturing molecule was the whole antibody and the antibody F(ab) fragment, respectively.

Spehar-Délèze|Anna-Maria|AM|
Julich|Sandra|S|
Gransee|Rainer|R|
Tomaso|Herbert|H|
Dulay|Samuel B|SB|
O'Sullivan|Ciara K|CK|

Electrochemiluminescence
Antibody fragment
Immunoassay
Biowarfare agent
Screen-printed gold array


Flunarizine exhibits in vitro efficacy against lymphoma and multiple myeloma cells.

Abstract:
BACKGROUND/AIM
Novel agents such as lenalidomide and bortezomib have significantly improved today's therapy of multiple myeloma. Despite recent innovations, new therapeutic options are needed. The Wingless-related integration site (WNT) pathway is aberrantly activated in lymphoma and myeloma and therefore renders WNT signaling molecules attractive for the development of targeted therapies. Flunarizine was used in this study as it has chemical features similar to those of other known WNT inhibitors and already proven proapoptotic properties in leukemia cells.

MATERIALS AND METHODS
The antitumor apoptotic effect of flunarizine at doses ranging from 0.1-200 μM was investigated on three human lymphoma cell lines, one murine and four human myeloma cell lines by 3'3-Dihexyloxacarbocyanine iodide and propidium iodide staining in flow cytometry.

RESULTS
Flunarizine induced significant apoptotic activity in all tested myeloma and lymphoma cell lines in a dose-dependent manner.

CONCLUSION
Our results reveal a significant selective induction of apoptosis by flunarizine and suggest an in vivo effect against lymphoma and myeloma.

Schmeel|Leonard Christopher|LC|
Schmeel|Frederic Carsten|FC|
Kim|Young|Y|
Blaum-Feder|Sabine|S|
Endo|Tomoyuki|T|
Schmidt-Wolf|Ingo G H|IG|

Flunarizine
lymphoma
multiple myeloma
WNT
pathway
cancer therapy


Strain-Modulated Bandgap and Piezo-Resistive Effect in Black Phosphorus Field-Effect Transistors.

Abstract: Energy bandgap largely determines the optical and electronic properties of a semiconductor. Variable bandgap therefore makes versatile functionality possible in a single material. In layered material black phosphorus, the bandgap can be modulated by the number of layers; as a result, few-layer black phosphorus has discrete bandgap values that are relevant for optoelectronic applications in the spectral range from red, in monolayer, to mid-infrared in the bulk limit. Here, we further demonstrate continuous bandgap modulation by mechanical strain applied through flexible substrates. The strain-modulated bandgap significantly alters the density of thermally activated carriers; we for the first time observe a large piezo-resistive effect in black phosphorus field-effect transistors (FETs) at room temperature. The effect opens up opportunities for future development of electromechanical transducers based on black phosphorus, and we demonstrate an ultrasensitive strain gauge constructed from black phosphorus thin crystals.

Zhang|Zuocheng|Z|0000-0001-7851-6101
Li|Likai|L|0000-0003-2907-8939
Horng|Jason|J|
Wang|Nai Zhou|NZ|
Yang|Fangyuan|F|
Yu|Yijun|Y|
Zhang|Yu|Y|
Chen|Guorui|G|0000-0002-4919-4796
Watanabe|Kenji|K|
Taniguchi|Takashi|T|
Chen|Xian Hui|XH|
Wang|Feng|F|
Zhang|Yuanbo|Y|

piezo-resistive effect
Black phosphorus
field-effect transistor
bandgap modulation
strain