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TALN research group at LS2N lab 12

34395405

Advances in the Development of Biomaterials for Endotoxin Adsorption in Sepsis.

Sepsis, a life-threatening and intractable disease without any specific treatment, is activated by endotoxin. Some attempts at removing endotoxin to treat sepsis from the blood circulation using different hemoperfusion cartridges have been proposed recently, but they have failed to reduce the mortality of severe septic patients. This review summarizes the latest advances in the development of endotoxin adsorbents. In particular, we highlight two critical parameters for endotoxin adsorbents when they are applied in blood purification: the dissociation constant and the maximum adsorption capacity. We also discuss potential challenges and research directions for the future development of endotoxin adsorbents.

['Yang|Qinbo|Q|', 'Li|Yupei|Y|', 'Tuohuti|Pazilaiti|P|', 'Qin|Zheng|Z|', 'Zhang|Zhuyun|Z|', 'Zhao|Weifeng|W|', 'Su|Baihai|B|']

2021

24106600

Ghrelin Does not Alter Aortic Intima-Media Thickness and Adipose Tissue Characteristics in Control and Obese Mice.

OBJECTIVE(S) Atherosclerosis is a chronic immune-inflammatory disease that generally leads to ischemic heart disease. Ghrelin has several modulatory effects on cardiovascular system. In this study, we investigated the effect of ghrelin on aortic intima-media thickness, size and the number of adipocyte cells in obese and control mice. MATERIALS AND METHODS This study was conducted on 24 male C57BL/6 mice. The animals were divided into four groups: control, obese (received high fat diet), control+ghrelin (injected with 100 µg/Kg subcutaneously, bid) and obese+ghrelin (n=6 each). After 10 days, animals were sacrificed and epididymal adipose tissue and thoracic aortae were removed. Adipocyte cell number, size and aortic intima-media thickness were evaluated. RESULTS Ghrelin did not change adipocyte cell number and size and aortic intima-media thickness in obese and control mice. In this study, high fat diet significantly decreased the number of adipocyte cells while increased their size (P<0.05). Ghrelin administration had no significant effect on adipocyte cell number and size in obese and control groups (P >0.05). In addition, it could not alter aortic intima-media thickness in both groups. CONCLUSION Although ghrelin has several cardiovascular effects, it seems that it could not alter the size and number of adipocyte cells and aortic intima-media thickness in diet-induced obese mice.

['Tahergorabi|Zoya|Z|', 'Rashidi|Bahman|B|', 'Khazaei|Majid|M|']

2013

34679908

Companion Animal Ownership and Mood States of University Students Majoring in Animal Sciences during the COVID-19 Pandemic in Japan.

COVID-19 caused great difficulties in many people's daily lives, including university students in Japan. This study examined whether living with companion animals and attachment to companion animals influence the moods of university students. Students answered a questionnaire, including demographic data, companion animal ownership, attachment to their companion animals, perceived difficulties from COVID-19, and Profile of Mood States 2 (POMS2) results. A total of 180 students answered the questionnaire. Stepwise multiple regression analyses were conducted to identify factors related to the total mood disturbance (TMD) score of the POMS2. In the regression model, perceived difficulties from COVID-19 and having a companion animal and a strong attachment to their companion animals were significantly correlated with TMD and served as the predictor variables. The first variable was positively related to TMD, whereas companion animal ownership with high attachment to their companion animals was negatively related to TMD. This finding indicated that companion animal ownership with high attachment to their companion animals would relate to a positive mood in university students majoring in animal sciences during the COVID-19 pandemic. However, because of the limited population in size and by the students' major, the results need to be interpreted as a possible effect of companion animals, and not as conclusive evidence to support the effects of animals.

['Namekata|Daiki|D|', 'Yamamoto|Mariko|M|']

2021

25443273

Pemetrexed in patients with thymic malignancies previously treated with chemotherapy.

PURPOSE Thymic malignancies are rare, with limited published trials of chemotherapy activity. We performed a retrospective analysis of pemetrexed activity in patients with thymic malignancies. METHODS Patients with unresectable histologically confirmed invasive, recurrent, or metastatic thymoma or thymic carcinoma seen at the Stanford Cancer Center between January 2005 and November 2013 were identified, and those who were treated with pemetrexed in the second-line setting and beyond were included in this analysis. RESULTS A total of 81 thymic malignancy patients were identified, of whom 16 received pemetrexed alone (N=14) or in combination (N=2). There were 10 patients (62.5%) with thymic carcinoma and 6 patients (37.5%) with thymoma. Among the 6 patients with thymoma, best response was 1 (17%) with a partial response (PR) and 5 (83%) with stable disease (SD). At a median follow-up of 21.2 months, the median PFS in the thymoma patients was 13.8 months (95% CI, 4.9-22.6 months) and the median OS was 20.1 months (95% CI, 16.4-23.9 months). Among the 10 patients with thymic carcinoma, best response to treatment was 1 (10%) PR, 5 (50%) SD, and 4 (40%) progressive disease (PD). At a median follow-up of 13.5 months, the median PFS in patients with thymic carcinoma was 6.5 months (95% CI, 0.2-12.8 months) and the median OS was 12.7 months (95% CI, 2.9-22.5 months). CONCLUSIONS This small retrospective study demonstrates modest pemetrexed activity and disease stabilization in thymic malignancies with a clinically meaningful duration, and supports previous reports of pemetrexed efficacy in these rare diseases.

['Liang|Ying|Y|', 'Padda|Sukhmani K|SK|', 'Riess|Jonathan W|JW|', 'West|Robert B|RB|', 'Neal|Joel W|JW|', 'Wakelee|Heather A|HA|']

2015

24924134

Single-cell imaging for the study of oncometabolism.

Metabolic profiling is commonly employed to investigate the global metabolic alterations of malignant cells or tissues. In the latter setting, neoplastic lesions are separated from adjacent, healthy tissues and their metabolites are quantified upon a chromatographic run coupled to mass spectrometry. Changes in the abundance of specific metabolites are then mapped on metabolic networks and the underlying metabolic circuitries are investigated as potential targets for the development of novel anticancer drugs. This approach, however, does not take into account the intrinsic heterogeneity of neoplastic lesions, which contain a large amount of non-transformed cells. To circumvent this issue, techniques have been developed that allow for the imaging of metabolites at the single-cell level. Here, we summarize established protocols that are suitable for imaging metabolites in animal cells (be them malignant or not) as well as in plant and prokaryotic cells. These methods are relevant for the study of the metabolic alterations that accompany oncogenesis and tumor progression.

['Svatoš|Aleš|A|', 'Ibáñez|Alfredo J|AJ|']

2014

29035338

Integrating Medication Therapy Management (MTM) Services Provided by Community Pharmacists into a Community-Based Accountable Care Organization (ACO).

(1) Background: As the U.S. healthcare system evolves from fee-for-service financing to global population-based payments designed to be accountable for both quality and total cost of care, the effective and safe use of medications is gaining increased importance. The purpose of this project was to determine the feasibility of integrating medication therapy management (MTM) services provided by community pharmacists into the clinical care teams and the health information technology (HIT) infrastructure for Minnesota Medicaid recipients of a 12-county community-based accountable care organization (ACO). (2) Methods: The continuous quality improvement evaluation methodology employed in this project was the context + mechanism = outcome (CMO) model to account for the fact that programs only work insofar as they introduce promising ideas, solutions and opportunities in the appropriate social and cultural contexts. Collaborations between a 12-county ACO and 15 community pharmacies in Southwest Minnesota served as the social context for this feasibility study of MTM referrals to community pharmacists. (3) Results: All 15 community pharmacy sites were integrated into the HIT infrastructure through Direct Secure Messaging, and there were 32 recipients who received MTM services subsequent to referrals from the ACO at 5 of the 15 community pharmacies over a 1-year implementation phase. (4) Conclusion: At the conclusion of this project, an effective electronic communication and MTM referral system was activated, and consideration was given to community pharmacists providing MTM in future ACO shared savings agreements.

['Isetts|Brian|B|0000-0002-7557-1479']

2017

33339581

Association of the Sp1 binding site and -1997 promoter variations in COL1A1 with osteoporosis risk: The application of meta-analysis and bioinformatics approaches offers a new perspective for future research.

As a complex disease, osteoporosis is influenced by several genetic markers. Many studies have examined the link between the Sp1 binding site +1245 G > T (rs1800012) and -1997 G > T (rs1107946) variations in the COL1A1 gene with osteoporosis risk. However, the findings of these studies have been contradictory; therefore, we performed a meta-analysis to aggregate additional information and obtain increased statistical power to more efficiently estimate this correlation. A meta-analysis was conducted with studies published between 1991-2020 that were identified by a systematic electronic search of the Scopus and Clarivate Analytics databases. Studies with bone mineral density (BMD) data and complete genotypes of the single-nucleotide variations (SNVs) for the overall and postmenopausal female population were included in this meta-analysis and analyzed using the R metaphor package. A relationship between rs1800012 and significantly decreased BMD values at the lumbar spine and femoral neck was found in individuals carrying the "ss" versus the "SS" genotype in the overall population according to a random effects model (p < 0.0001). Similar results were also found in the postmenopausal female population (p = 0.003 and 0.0002, respectively). Such findings might be an indication of increased osteoporosis risk in both studied groups in individuals with the "ss" genotype. Although no association was identified between the -1997 G > T and low BMD in the overall population, those individuals with the "GT" genotype showed a higher level of BMD than those with "GG" in the subgroup analysis (p = 0.007). To determine which transcription factor (TF) might bind to the -1997 G > T in COL1A1, 45 TFs were identified based on bioinformatics predictions. According to the GSE35958 microarray dataset, 16 of 45 TFs showed differential expression profiles in osteoporotic human mesenchymal stem cells relative to normal samples from elderly donors. By identifying candidate TFs for the -1997 G > T site, our study offers a new perspective for future research.

['Moradifard|Shirin|S|', 'Hoseinbeyki|Moslem|M|', 'Emam|Mohammad Mehdi|MM|', 'Parchiniparchin|Fatemehsadat|F|', 'Ebrahimi-Rad|Mina|M|']

2020

32569747

Dual soluble epoxide hydrolase inhibitor/PPAR-γ agonist attenuates renal fibrosis.

Renal fibrosis is a contributor to chronic kidney disease and an important predictor of long-term prognosis. We developed a dual soluble epoxide hydrolase inhibitor-PPAR-γ agonist (sEHi/PPAR-γ), RB394, and investigated its ability to attenuate renal fibrosis in a mouse unilateral ureteral obstruction (UUO) model. RB394 efficacy was compared to an sEH inhibitor (sEHi), a PPAR-γ agonist rosiglitazone (Rosi), or their combination (sEHi + Rosi). All interventional treatments were administrated in drinking water 3 days after UUO induction surgery and continued for 7 days. UUO mice developed renal fibrosis with higher collagen formation and RB394 significantly attenuated fibrosis (P < 0.05). Renal expression of α-smooth muscle actin (α-SMA) was elevated in UUO mice and all treatments except sEHi significantly attenuated renal α-SMA expression. Renal mRNA expression fibrotic and fibrosis regulators were higher in UUO mice and RB394 and sEHi + Rosi treatments attenuated their expression. Renal inflammation was evident in UUO mice with increased infiltration of CD45 and F4/80 positive cells. RB394 and sEHi + Rosi treatments attenuated renal inflammation in UUO mice. UUO mice had renal tubular and vascular injury. Renal tubular and vascular injuries were attenuated to a greater extent by RB394 and sEHi + Rosi than sEHi or Rosi treatment alone. Renal mRNA expression of oxidative stress markers were significantly higher in UUO mice (P < 0.05). RB394 and sEHi + Rosi attenuated expression of oxidative stress markers to a greater extent than other interventional treatments (P < 0.05). These findings demonstrate that RB394 can attenuate renal fibrosis by reducing renal inflammation, oxidative stress, tubular injury, and vascular injury. In conclusion, RB394 demonstrates exciting potential as a therapeutic for renal fibrosis and chronic kidney disease.

['Stavniichuk|Anna|A|', 'Hye Khan|Md Abdul|MA|', 'Yeboah|Michael M|MM|', 'Chesnik|Marla A|MA|', 'Jankiewicz|Wojciech K|WK|', 'Hartmann|Markus|M|', 'Blöcher|René|R|', 'Kircher|Theresa|T|', 'Savchuk|Olexiy|O|', 'Proschak|Ewgenij|E|', 'Imig|John D|JD|']

2020

34571535

Deep learning in retrosynthesis planning: datasets, models and tools.

In recent years, synthesizing drugs powered by artificial intelligence has brought great convenience to society. Since retrosynthetic analysis occupies an essential position in synthetic chemistry, it has received broad attention from researchers. In this review, we comprehensively summarize the development process of retrosynthesis in the context of deep learning. This review covers all aspects of retrosynthesis, including datasets, models and tools. Specifically, we report representative models from academia, in addition to a detailed description of the available and stable platforms in the industry. We also discuss the disadvantages of the existing models and provide potential future trends, so that more abecedarians will quickly understand and participate in the family of retrosynthesis planning.

['Dong|Jingxin|J|', 'Zhao|Mingyi|M|', 'Liu|Yuansheng|Y|', 'Su|Yansen|Y|', 'Zeng|Xiangxiang|X|']

2021

33335792

Enhancing cardiac reprogramming via synthetic RNA oligonucleotides.

Reprogramming scar fibroblasts into new heart muscle cells has the potential to restore function to the injured heart. However, the effectiveness of reprogramming is notably low. We have recently demonstrated that the effectiveness of reprogramming fibroblasts into heart muscle cells (cardiomyocytes) is increased by the addition of RNA-sensing receptor ligands. Clinical use of these ligands is problematic due to their ability to induce adverse inflammatory events. To overcome this issue, we sought to determine whether synthetic analogs of natural RNA-sensing receptor ligands, which avoid generating inflammatory insults and are nuclease resistant, would similarly enhance fibroblast reprogramming into cardiomyocytes. Indeed, one such stabilized RNA, ICR2, increased the expression of cardiomyocyte-specific mRNAs in reprogrammed fibroblasts. Moreover, ICR2 enhanced the ability of reprogramming factors to produce cardiomyocytes with mature sarcomeres. Knockdown assays indicated that the effects of ICR2 were mediated by the RNA-sensing receptors Rig-I and TLR3. In addition, ICR2 reduced the effective dose and number of reprogramming factors needed for efficient reprogramming. In summary, the synthetic RNA oligonucleotide ICR2 is a potential therapeutic agent to enhance cardiac reprogramming efficiency.

['Hu|Jiabiao|J|', 'Hodgkinson|Conrad P|CP|', 'Pratt|Richard E|RE|', 'Lee|JaeWoo|J|', 'Sullenger|Bruce A|BA|', 'Dzau|Victor J|VJ|']

2021

34500893

Determination of the Spatial Anisotropy of the Surface MicroStructures of Different Implant Materials: An Atomic Force Microscopy Study.

Many biomaterials' surfaces exhibit directional properties, i.e., possess spatial anisotropy on a range of spatial scales spanning from the domain of the naked eye to the sub-micrometer level. Spatial anisotropy of surface can influence the mechanical, physicochemical, and morphological characteristics of the biomaterial, thus affecting its functional behavior in relation, for example, to the host tissue response in regenerative processes, or to the efficacy of spatially organized surface patterns in avoiding bacterial attachment. Despite the importance of the availability of quantitative data, a comprehensive characterization of anisotropic topographies is generally a hard task due to the proliferation of parameters and inherent formal complications. This fact has led so far to excessive simplification that has often prevented researchers from having comparable results. In an attempt to overcome these issues, in this work a systematic and multiscale approach to spatial anisotropy is adopted, based on the determination of only two statistical parameters of surface, namely the texture aspect ratio S and the roughness exponent H, extracted from atomic force microscopy images of the surface. The validity on this approach is tested on four commercially available implant materials, namely titanium alloy, polyethylene, polyetheretherketone and polyurethane, characterized by textured surfaces obtained after different machining. It is found that the "two parameters" approach is effective in describing the anisotropy changes on surfaces with complex morphology, providing a simple quantitative route for characterization and design of natural and artificial textured surfaces at spatial scales relevant to a wide range of bio-oriented applications.

['Gambardella|Alessandro|A|', 'Marchiori|Gregorio|G|0000-0002-2171-1851', 'Maglio|Melania|M|', 'Russo|Alessandro|A|', 'Rossi|Chiara|C|', 'Visani|Andrea|A|', 'Fini|Milena|M|']

2021

26521149

Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin.

OBJECTIVES Conflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied. METHODS Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR(-/-);ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0mg/kg body weight (BW)/d recombinant leptin over 12weeks starting at 8weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red O staining. Furthermore, glucose homeostasis, lipid metabolism, and liver function including tissue studies were assessed in all animals. RESULTS Leptin treatment dose-dependently decreased BW in LDLR(-/-);ob/ob mice as compared to saline. Mice in the 0.1 and 0.5mg/kgBW/d groups remained heavier (i.e. subphysiological leptin dose) and in the 3.0mg/kgBW/d group had similar weight (i.e. physiological leptin dose) as compared to non-leptin-deficient LDLR(-/-) animals. Recombinant leptin dose-dependently reduced plaque area in the aortic root and the BCA by 36% and 58%, respectively. Leptin-mediated reductions of plasma total and LDL-cholesterol (Chol) remained independent predictors for aortic root plaque area. Chol content in liver, as well as hepatic expression of key lipid and proinflammatory genes, were dose-dependently regulated by leptin. Furthermore, leptin treatment increased circulating levels and adipose tissue mRNA expression of the adipokine adiponectin. CONCLUSIONS Leptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hypercholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin.

['Hoffmann|Annett|A|', 'Ebert|Thomas|T|', 'Klöting|Nora|N|', 'Dokas|Janine|J|', 'Jeromin|Franziska|F|', 'Jessnitzer|Beate|B|', 'Burkhardt|Ralph|R|', 'Fasshauer|Mathias|M|', 'Kralisch|Susan|S|']

2016

33007937

Cicer arietinum L. Sprouts' Influence on Mineralization of Saos-2 and Migration of MCF-7 Cells.

In the present study, we investigated the biological activity of four extracts obtained from Cicer arietinum L. sprouts. The fermentation of the sprouts with Lactobacillus casei and their incubation with β-glucosidase elevated the concentrations of isoflavonoids, especially coumestrol, formononetin and biochanin A. To study the biological activity of C. arietinum, the human osteosarcoma Saos-2 and human breast cancer MCF-7 cell lines were used. The extracts obtained from fermented sprouts exhibited the strongest ability to decrease intracellular oxidative stress in both types of cells. They augmented mineralization and alkaline phosphatase activity in Saos-2 cells, as well as diminished the secretion of interleukin-6 and tumor necrosis factor α. Simultaneously, the extracts, at the same doses, inhibited the migration of MCF-7 cells. On the other hand, elevated concentrations of C. arietinum induced apoptosis in estrogen-dependent MCF-7 cells, while lower doses stimulated cell proliferation. These results are important for carefully considering the use of fermented C. arietinum sprouts as a dietary supplement component for the prevention of osteoporosis.

['Zakłos-Szyda|Małgorzata|M|0000-0001-8341-1654', 'Gałązka-Czarnecka|Ilona|I|0000-0001-6039-2796', 'Grzelczyk|Joanna|J|', 'Budryn|Grażyna|G|0000-0002-8050-3702']

2020

33693154

Goal-Oriented Sequential Combination Therapy Evaluated Using Cardiopulmonary Exercise Parameters for the Treatment of Newly Diagnosed Pulmonary Arterial Hypertension　- Goal-Oriented Therapy Evaluated by Cardiopulmonary Exercise Testing for Pulmonary Arterial Hypertension (GOOD EYE).

Many treatment options are available for pulmonary arterial hypertension (PAH), but specific recommendations for long-term treatment are unavailable. We compared prognosis in PAH patients receiving goal-oriented, sequential combination therapy evaluated using cardiopulmonary exercise testing (CPX) parameters or conventional empiric therapy. The Goal-Oriented Therapy Evaluated by Cardiopulmonary Exercise Testing for Pulmonary Arterial Hypertension (GOOD EYE) study was a multicenter, retrospective/prospective study in which a total of 129 patients with newly diagnosed PAH were enrolled (goal-oriented sequential combination therapy, n=42; conventional empiric therapy, n=87). Patients in the goal-oriented therapy group received sequential combination therapy, the efficacy of which was regularly evaluated using CPX parameters. Patients in the conventional empiric therapy group received conventional empiric therapy. The primary endpoint was cardiovascular death. In the goal-oriented therapy group, plasma brain natriuretic peptide, mean pulmonary arterial pressure, pulmonary vascular resistance, and 6-min walk test were significantly improved at 12 months compared with baseline. Survival in the goal-oriented therapy group at 1, 2, and 3 years (97.6%, 95.2%, and 86.0%, respectively) tended to be higher than that in the conventional empiric therapy group (P=0.082). Goal-oriented sequential combination therapy evaluated using CPX parameters may be associated with a favorable prognosis compared with conventional empiric therapy in patients with newly diagnosed PAH.

['Hirashiki|Akihiro|A|', 'Kondo|Takahisa|T|', 'Adachi|Shiro|S|', 'Nakano|Yoshihisa|Y|', 'Kamimura|Yoshihiro|Y|', 'Shimokata|Shigetake|S|', 'Okumura|Naoki|N|', 'Shimizu|Atsuya|A|', 'Washimi|Yukihiko|Y|', 'Arai|Hidenori|H|', 'Murohara|Toyoaki|T|', '|||']

2019

33509304

Prognostic value of metabolic tumor volume and total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with localized primary gastrointestinal stromal tumors.

BACKGROUND This study aimed to evaluate the prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with localized primary gastrointestinal stromal tumors (GISTs) and to compare the predictive values of 18F-FDG PET/CT parameters with those of clinicopathological prognostic factors. METHODS Sixty-two localized GIST patients who underwent staging with 18F-FDG PET/CT from January 2007 to December 2013 before surgery were retrospectively enrolled. A volume of interest with a standardized uptake value (SUV) threshold of 2.5 was used to determine the metabolic tumor volume (MTV) and total lesion glycolysis (TLG). These metabolic indices, along with the maximum SUV (SUVmax), were analyzed to evaluate recurrence-free survival (RFS). Other significant clinical and pathologic indices were also retrospectively reviewed for RFS analysis. RESULTS Patients were followed up for a median of 42.0 months (range, 5.6-111.5). During the follow-up period, 13 patients (21.0%) experienced disease recurrence. In univariate analysis, tumor size (> 5 cm), mitotic count (> 5/high-power field), modified National Institutes of Health (NIH) consensus criteria, adjuvant imatinib treatment, SUVmax (≥ 7.04), MTV (≥ 50.76 cm3), and TLG (≥ 228.79 g) were significant prognostic factors affecting RFS (p < 0.05). In multivariate analysis, only MTV (hazard ratio, 17.69; 95% confidence interval [CI], 2.03-154.17, p = 0.009) and TLG (hazard ratio, 20.48; 95% CI, 2.19-191.16, p = 0.008) were independent prognostic factors for RFS. The 5-year RFS rates were 96.4% and 96.6% in patients with a low MTV and TLG and 27.3% and 23.6% in patients with a high MTV and TLG, respectively (p < 0.001). CONCLUSION MTV and TLG are independent prognostic factors for predicting recurrence in patients with localized primary GIST. Patients with a high MTV or TLG are at risk for poor prognosis and should be closely observed for disease recurrence.

['Hwang|Sang Hyun|SH|', 'Jung|Minkyu|M|', 'Jeong|Yong Hyu|YH|', 'Jo|KwanHyeong|K|', 'Kim|Soyoung|S|', 'Wang|Jiyoung|J|', 'Cho|Arthur|A|http://orcid.org/0000-0001-8670-2473']

2021

31871862

Extracellular Nanomatrix-Induced Self-Organization of Neural Stem Cells into Miniature Substantia Nigra-Like Structures with Therapeutic Effects on Parkinsonian Rats.

Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson's disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN-like structures (mini-SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self-organization of mini-SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self-organization of the mini-SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini-SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self-organization of region-specific and functional brain-like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD.

['Zhang|Shiqing|S|https://orcid.org/0000-0002-0785-5461', 'Sun|Peng|P|', 'Lin|Kaili|K|', 'Chan|Florence Hiu Ling|FHL|', 'Gao|Qi|Q|', 'Lau|Wai Fung|WF|', 'Roy|Vellaisamy A L|VAL|', 'Zhang|Hongqi|H|', 'Lai|King Wai Chiu|KWC|', 'Huang|Zhifeng|Z|https://orcid.org/0000-0002-9613-9423', 'Yung|Ken Kin Lam|KKL|https://orcid.org/0000-0002-9588-2573']

2019

30414707

An acute encephalopathy with reduced diffusion in BRAF-associated cardio-facio-cutaneous syndrome.

BACKGROUND Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder characterized by cardiovascular anomalies, dysmorphic faces, ectodermal abnormalities and developmental delays. Mutations in BRAF and other RAS-MAPK pathway-associated genes are commonly identified in patients with CFCS. While this molecular pathway is known to be associated with neuro-inflammatory conditions, only one case with CFCS has been reported thus far to develop acute encephalopathy in childhood. CASE REPORT A 3-year-old boy with dysmorphic features and mild psychomotor delay developed acute encephalopathy. After a 45-min long, generalized seizure, the magnetic resonance imaging revealed that the restricted diffusion signals spread to the bilateral subcortical white matters on day 1 of illness. Despite the 14 days of intensive care, the acute symptoms of encephalopathy left him intractable epilepsy and severe neurocognitive impairments. The whole-exome sequencing analysis identified a de novo heterozygous mutation of BRAF (NM_004333:p.Thr241Met) in this case. CONCLUSION The present case suggests that the hyperactive condition of ERK signals might augment the development of acute encephalopathy and post-encephalopathic epilepsy in childhood.

['Okuzono|Sayaka|S|', 'Fukai|Ryoko|R|', 'Noda|Marie|M|', 'Miyake|Noriko|N|', 'Lee|Sooyoung|S|', 'Kaku|Noriyuki|N|', 'Sanefuji|Masafumi|M|', 'Akamine|Satoshi|S|', 'Kanno|Shunsuke|S|', 'Ishizaki|Yoshito|Y|', 'Torisu|Hiroyuki|H|', 'Kira|Ryutaro|R|', 'Matsumoto|Naomichi|N|', 'Sakai|Yasunari|Y|', 'Ohga|Shouichi|S|']

2019

28299829

Thermally Induced Crystallization of High Quality CH3 NH3 PbI3 Film with Large Grains for Highly Efficient Perovskite Solar Cells.

Recently, fully covered and smooth perovskite films could be fabricated by optimized coating methods; however, it is still hard to prepare perovskite films with large grain sizes and high crystallinity. Given the fact that thermal energy can promote crystallization, we combine high-temperature crystallization with the application of a solvent featuring a high boiling point, in order to produce high quality perovskite films with micrometer-sized grains. We further investigated the temperature dependence of the thermally induced synthetic strategy, whereby the grains become larger as the temperature is elevated. After solar cell device fabrication, the efficiency of the best cell can attain a high value of 15.53 % with reduced hysteresis behavior.

['Hou|Yu|Y|', 'Yang|Shuang|S|http://orcid.org/0000-0002-8244-3002', 'Chen|Xiao|X|', 'Li|Chunzhong|C|', 'Zhao|Huijun|H|http://orcid.org/0000-0003-3794-4497', 'Yang|Hua Gui|HG|']

2017

29540407

Macroeconomic costs of the unmet burden of surgical disease in Sierra Leone: a retrospective economic analysis.

OBJECTIVES The Lancet Commission on Global Surgery estimated that low/middle-income countries will lose an estimated cumulative loss of US$12.3 trillion from gross domestic product (GDP) due to the unmet burden of surgical disease. However, no country-specific data currently exist. We aimed to estimate the costs to the Sierra Leone economy from death and disability which may have been averted by surgical care. DESIGN We used estimates of total, met and unmet need from two main sources-a cluster randomised, cross-sectional, countrywide survey and a retrospective, nationwide study on surgery in Sierra Leone. We calculated estimated disability-adjusted life years from morbidity and mortality for the estimated unmet burden and modelled the likely economic impact using three different methods-gross national income per capita, lifetime earnings foregone and value of a statistical life. RESULTS In 2012, estimated, discounted lifetime losses to the Sierra Leone economy from the unmet burden of surgical disease was between US$1.1 and US$3.8 billion, depending on the economic method used. These lifetime losses equate to between 23% and 100% of the annual GDP for Sierra Leone. 80% of economic losses were due to mortality. The incremental losses averted by scale up of surgical provision to the Lancet Commission target of 80% were calculated to be between US$360 million and US$2.9 billion. CONCLUSION There is a large economic loss from the unmet need for surgical care in Sierra Leone. There is an immediate need for massive investment to counteract ongoing economic losses.

['Grimes|Caris E|CE|0000-0002-1662-5799', 'Quaife|Matthew|M|0000-0001-9291-1511', 'Kamara|Thaim B|TB|', 'Lavy|Christopher B D|CBD|', 'Leather|Andy J M|AJM|', 'Bolkan|Håkon A|HA|']

2018

26041032

Avian thermoregulation in the heat: scaling of heat tolerance and evaporative cooling capacity in three southern African arid-zone passerines.

Many birds can defend body temperature (Tb) far below air temperature (Ta) during acute heat exposure, but relatively little is known about how avian heat tolerance and evaporative cooling capacity varies with body mass (Mb), phylogeny or ecological factors. We determined maximum rates of evaporative heat dissipation and thermal end points (Tb and Ta associated with thermoregulatory failure) in three southern African ploceid passerines, the scaly-feathered weaver (Sporopipes squamifrons, Mb≈10 g), sociable weaver (Philetairus socius, Mb≈25 g) and white-browed sparrow-weaver (Plocepasser mahali, Mb≈40 g). Birds were exposed to a ramped profile of progressively increasing Ta, with continuous monitoring of behaviour and Tb used to identify the onset of severe hyperthermia. The maximum Ta birds tolerated ranged from 48°C to 54°C, and was positively related to Mb. Values of Tb associated with severe heat stress were in the range of 44 to 45°C. Rates of evaporative water loss (EWL) increased rapidly when Ta exceeded Tb, and maximum evaporative heat dissipation was equivalent to 141-222% of metabolic heat production. Fractional increases in EWL between Ta<40°C and the highest Ta reached by each species were 10.8 (S. squamifrons), 18.4 (P. socius) and 16.0 (P. mahali). Resting metabolic rates increased more gradually with Ta than expected, probably reflecting the very low chamber humidity values we maintained. Our data suggest that, within a taxon, larger species can tolerate higher Ta during acute heat stress.

['Whitfield|Maxine C|MC|', 'Smit|Ben|B|', 'McKechnie|Andrew E|AE|', 'Wolf|Blair O|BO|']

2015

34658323

The impact a Mediterranean Diet in the third trimester of pregnancy has on neonatal body fat percentage.

Maternal diet during pregnancy has long been recognised as an important determinant of neonatal outcomes and child development. Infant body composition is a potentially modifiable risk factor for predicting future health and metabolic disease. Utilising the Mediterranean Diet Score, this study focused on how different levels of Mediterranean Diet adherence (MDA) in pregnancy influence body fat percentage of the infant. Information on 458 pregnant women in their third trimester of pregnancy and their infants was obtained from The ORIGINS Project. The data included MDA score, body composition measurements using infant air displacement plethysmography (PEA POD), pregnancy, and birth information. Infants born to mothers with high MDA had a body fat percentage of 11.3%, whereas infants born to mothers with low MDA had a higher body fat percentage of 13.3% (p = 0.010). When adjusted for pre-pregnancy body mass index and infant sex, a significant result remained between high vs. low MDA and infant fat mass (FM) (2.5% less FM p = 0.016). This study suggests that high MDA in pregnancy was associated with a reduced body fat percentage in the newborn. Future studies are needed to understand whether small but significant changes in FM persist throughout childhood.

['Ashwin|D|D|https://orcid.org/0000-0002-5274-279X', 'Gibson|L|L|', 'Hagemann|E|E|', "D'Vaz|N|N|", 'Bear|N|N|', 'Silva|D|D|']

2021

34422371

Diagnostic performance of DNA microarray for detecting rifampicin and isoniazid resistance in Mycobacterium tuberculosis.

Background While rifampicin (RFP) and isoniazid (INH) are the most commonly used first-line antituberculosis drugs, multidrug resistance in Mycobacterium tuberculosis poses a threat to the success of tuberculosis (TB) control programs. Clinical practice guidelines and expert consensuses recommend drug susceptibility testing (DST) before the initiation of antituberculosis treatment. However, traditional DST is time-consuming and has high requirements for laboratory conditions. The recently developed molecular diagnostic techniques, such as DNA microarray, offer new options. We thus investigated the diagnostic value of DNA microarray in detecting RFP + INH-resistant TB, with an attempt to identify simple, efficient, and accurate drug-resistant TB testing methods. Methods The clinical features and DST results of patients diagnosed with pulmonary tuberculosis by Bactec MGIT 960 liquid culture system (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) who received DNA microarray analysis in our center from July 2019 to July 2020 were retrospectively analyzed. Level of agreement between liquid culture and DNA microarray technology was assessed by using the Cohen kappa coefficient. With the results of liquid culture as the gold standard, the sensitivity and specificity of the DNA microarray were calculated, and the receiver operating characteristic (ROC) curves were used to assess the diagnostic values of the DNA microarray in detecting RFP + INH-resistant TB. Results A total of 825 patients were enrolled. The sensitivity and specificity of DNA microarray were 0.84 and 0.94, respectively, in the detection of RFP resistance, with an area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87-0.91)] and a Cohen kappa coefficient of 0.78 (95% CI: 0.72-0.83). For INH resistance, the sensitivity and specificity of the DNA microarray were 0.73 and 0.97, respectively, with an AUC of 0.85 (95% CI: 0.82-0.87) and a Cohen kappa coefficient of 0.75 (95% CI: 0.70-0.80). Conclusions The DNA microarray had high specificity and sensitivity in detecting RFP + INH-resistant TB. As a rapid, accurate, and practical technique, it can be routinely performed in clinical laboratories.

['Sun|Bingqi|B|', 'Sun|Ying|Y|']

2021

31077133

The protective effect of isoniazid preventive therapy on tuberculosis incidence among HIV positive patients receiving ART in Ethiopian settings: a meta-analysis.

BACKGROUND Tuberculosis (TB) and HIV makeup a deadly synergy of infectious disease, and the combined effect is apparent in resource limited countries like Ethiopia. Previous studies have demonstrated inconsistent results about the protective effect of isoniazid preventive therapy (IPT) on active TB incidence among HIV positive patients receiving ART. Therefore, the aim of this meta-analysis was, first, to determine the protective effect of IPT on active tuberculosis incidence, and second, to assess the pooled incidence of active TB among HIV positive patients taking ART with and without IPT intervention in Ethiopia. METHODS PubMed, Google scholar and Cochran library databases were searched from April 1 to 30, 2018. Two independent authors explored and assessed studies for eligibility, and extracted data based on predefined criteria. Studies that reported TB incidence among HIV positive patients taking ART in Ethiopia with and without IPT concomitant intervention, and with a clear stratified data on the incidence of TB based on the duration of IPT intervention were selected. A random effects model was used to estimate risk ratios and the pooled incident TB with the respective 95% confidence intervals. RESULTS We identified 7 suitable studies in this analysis. Accordingly, IPT reduced the risk of TB incidence by 74%, risk ratio (RR) 0.26 (95% CI; 0.16-0.43%), compared to no IPT group. Moreover, IPT for 12 months reduced incident TB by 91% (RR: 0.09, 95% CI: 0.04 to 0.21), whereas 6 months IPT averted TB incidence by 63% (RR: 0.37, 95% CI: 0.26 to 0.52). The overall pooled incident TB among HIV infected patients receiving ART was 10.30% (95% CI; 7.57-13.02%). Specifically, incident TB among study cohorts with and without IPT was 3.79% (95% CI; 2.03-5.55%) and 16.32% (95% CI; 11.57-21.06%) respectively. CONCLUSION IPT reduced the risk of incident TB among HIV positive patients receiving ART in Ethiopian settings. Moreover, the duration of IPT intervention has effect on its protective role. Thus, scaling up the isoniazid preventive therapy program and its strict compliance is necessary to avert HIV fueled tuberculosis. STUDY PROTOCOL REGISTRATION CRD42018090804.

['Geremew|Demeke|D|http://orcid.org/0000-0001-8493-1512', 'Endalamaw|Aklilu|A|', 'Negash|Markos|M|', 'Eshetie|Setegn|S|', 'Tessema|Belay|B|']

2019

32030318

Alternative splicing in tea plants was extensively triggered by drought, heat and their combined stresses.

Drought and heat stresses can influence the expressions of genes, and thereby affect the growth and development of plants. Alternative splicing (AS) of genes plays crucial roles through increasing transcriptome diversity in plant stress responses. Tea plants, widely cultivated in the tropics and subtropics, are often simultaneously exposed to drought and heat stresses. In the present study, we performed a global transcriptome of tea leaves treated with drought, heat or their combination. In total, 19,019, 20,025 and 20,253 genes underwent AS in response to drought (DT), heat (HT) and their combined stress (HD), respectively, of which 12,178, 11,912 and 14,413 genes differentially spliced in response to DT, HT and HD, respectively. Also, 2,447 specific differentially spliced genes (DSGs) were found only in response to HD. All DSGs accounted for  48% of the annotated genes in tea tree genome. Comparison of DSGs and differentially expressive genes (DEGs) showed that the proportions of HT and HD-induced DSGs were 13.4% and 9.2%, while the proportion of DT increased to 28.1%. Moreover, the DEG-DSG overlapped genes tended to be enriched in a wide large of pathways in response to DT. The results indicated that the AS of genes in tea leaves was extensively triggered by drought, heat and their combined stresses. In addition, the AS enhanced the transcriptome adaption in response to drought and heat stresses, and the AS also provoked specific molecular functions in response to drought and heat synergy stress. The study might have practical significance for molecular genetic breeding of tea plants with stress resistance.

['Ding|Yiqian|Y|', 'Wang|Yu|Y|', 'Qiu|Chen|C|', 'Qian|Wenjun|W|', 'Xie|Hui|H|', 'Ding|Zhaotang|Z|']

2020

29977499

The role of mitogen-activated protein kinase-extracellular receptor kinase pathway in female fertility outcomes: a focus on pituitary gonadotropins regulation.

Mammalian reproduction systems are largely regulated by the secretion of two gonadotropins, that is, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The main action of LH and FSH on the ovary is to stimulate secretion of estradiol and progesterone, which play an important role in the ovarian function and reproductive cycle control. FSH and LH secretions are strictly controlled by the gonadotropin-releasing hormone (GnRH), which is secreted from the hypothalamus into the pituitary vascular system. Maintaining normal secretion of LH and FSH is dependent on pulsatile secretion of GnRH. Extracellular signal-regulated kinase (ERK) proteins, as the main components of mitogen-activated protein kinase (MAPK) signaling pathways, are involved in the primary regulation of GnRH-stimulated transcription of the gonadotropins' α subunit in the pituitary cells. However, GnRH-stimulated expression of the β subunit has not yet been reported. Furthermore, GnRH-mediated stimulation of ERK1 and ERK2 leads to several important events such as cell proliferation and differentiation. In this review, we briefly introduce the relationship between ERK signaling and gonadotropin secretion, and its importance in female infertility.

['Kahnamouyi|Samira|S|', 'Nouri|Mohammad|M|', 'Farzadi|Laya|L|', 'Darabi|Masoud|M|', 'Hosseini|Vahid|V|', 'Mehdizadeh|Amir|A|https://orcid.org/0000-0002-3029-4172']

2018

24467902

Identification and validation of promoters and cis-acting regulatory elements.

Studies of promoters that largely regulate gene expression at the transcriptional level are crucial for improving our basic understanding of gene regulation and will expand the toolbox of available promoters for use in plant biotechnology. In this review, we present a comprehensive analysis of promoters and their underlying mechanisms in transcriptional regulation, including epigenetic marks and chromatin-based regulation. Large-scale prediction of promoter sequences and their contributing cis-acting elements has become routine due to recent advances in transcriptomic technologies and genome sequencing of several plants. However, predicted regulatory sequences may or may not be functional and demonstration of the contribution of the element to promoter activity is essential for confirmation of regulatory sequences. Synthetic promoters and introns provide useful approaches for functional validation of promoter sequences. The development and improvement of gene expression tools for rapid, efficient, predictable, and high-throughput analysis of promoter components will be critical for confirmation of the functional regulatory element sequences identified through transcriptomic and genomic analyses.

['Hernandez-Garcia|Carlos M|CM|', 'Finer|John J|JJ|']

2014

28726571

Primary Blast Causes Delayed Effects without Cell Death in Shell-Encased Brain Cell Aggregates.

Previous work in this laboratory used underwater explosive exposures to isolate the effects of shock-induced principle stress without shear on rat brain aggregate cultures. The current study has utilized simulated air blast to expose aggregates in suspension and enclosed within a spherical shell, enabling the examination of a much more complex biomechanical insult. Culture medium-filled spheres were exposed to single pulse overpressures of 15-30 psi (∼6-7 msec duration) and measurements within the sphere at defined sites showed complex and spatially dependent pressure changes. When brain aggregates were exposed to similar conditions, no cell death was observed and no changes in several commonly used biomarkers of traumatic brain injury (TBI) were noted. However, similarly to underwater blast, immediate and transient increases in the protein kinase B signaling pathway were observed at early time-points (3 days). In contrast, the oligodendrocyte marker 2',3'-cyclic nucleotide 3'-phosphodiesterase, as well as vascular endothelial growth factor, both displayed markedly delayed (14-28 days) and pressure-dependent responses. The imposition of a spherical shell between the single pulse shock wave and the target brain tissue introduces greatly increased complexity to the insult. This work shows that brain tissue can not only discriminate the nature of the pressure changes it experiences, but that a portion of its response is significantly delayed. These results have mechanistic implications for the study of primary blast-induced TBI and also highlight the importance of rigorously characterizing the actual pressure variations experienced by target tissue in primary blast studies.

['Sawyer|Thomas W|TW|', 'Ritzel|David V|DV|', 'Wang|Yushan|Y|', 'Josey|Tyson|T|', 'Villanueva|Mercy|M|', 'Nelson|Peggy|P|', 'Song|Yanfeng|Y|', 'Shei|Yimin|Y|', 'Hennes|Grant|G|', 'Vair|Cory|C|', 'Parks|Steve|S|', 'Fan|Changyang|C|', 'McLaws|Lori|L|']

2018

32781001

Dynamic analysis of 4E-BP1 phosphorylation in neurons with Tsc2 or Depdc5 knockout.

TSC1 or TSC2 mutations cause Tuberous Sclerosis Complex (TSC), and lead to mechanistic target of rapamycin (mTOR) hyperactivation evidenced by hyperphosphorylation of ribosomal S6 protein and 4-elongation factor binding protein 1 (4E-BP1). Amino acid (AA) levels modulate mTOR-dependent S6 and 4E-BP1 phosphorylation in non-neural cells, but this has not been comprehensively investigated in neurons. The effects of AA levels on mTOR signaling and S6 and 4E-BP1 phosphorylation were analyzed in Tsc2 and Depdc5 (a distinct mTOR regulatory gene associated with epilepsy) CRISPR-edited Neuro2a (N2a) cells and differentiated neurons. Tsc2 or Depdc5 knockout (KO) led to S6 and 4E-BP1 hyperphosphorylation and cell soma enlargement, but while Tsc2 KO N2a cells exhibited reduced S6 phosphorylation (Ser240/244) and cell soma size after incubation in AA free (AAF) media, Depdc5 KO cells did not. Using a CFP/YFP FRET-biosensor coupled to 4E-BP1, we assayed 4E-BP1 phosphorylation in living N2a cells and differentiated neurons following Tsc2 or Depdc5 KO. AAF conditions reduced 4E-BP1 phosphorylation in Tsc2 KO N2a cells but had no effect in Depdc5 KO cells. Rapamycin blocked S6 protein phosphorylation but had no effect on 4E-BP1 phosphorylation, following either Tsc2 or Depdc5 KO. Confocal imaging demonstrated that AAF media promoted movement of mTOR off the lysosome, functionally inactivating mTOR, in Tsc2 KO but not Depdc5 KO cells, demonstrating that AA levels modulate lysosomal mTOR localization and account, in part, for differential effects of AAF conditions following Tsc2 versus Depdc5 KO. AA levels and rapamycin differentially modulate S6 and 4E-BP1 phosphorylation and mTOR lysosomal localization in neurons following Tsc2 KO versus Depdc5 KO. Neuronal mTOR signaling in mTOR-associated epilepsies may have distinct responses to mTOR inhibitors and to levels of cellular amino acids.

['Iffland|Philip H|PH|', 'Barnes|Allan E|AE|', 'Baybis|Marianna|M|', 'Crino|Peter B|PB|']

2020

27033944

Long noncoding RNA POU6F2-AS2 is associated with oesophageal squamous cell carcinoma.

Oesophageal carcinoma is one of the most lethal cancer types in the world, especially in some part of China. Oesophageal squamous cell carcinoma (OSCC) is a major subtype, which has been shown to be associated with unhealthy diet habit, smoking, environmental carcinogens etc. The OSCC often progress slowly, however, it is often diagnosed at an advanced stage. Thus it is imperative to elucidate the molecular mechanisms involved in the initiation and progression of OSCC. Long noncoding RNAs (lncRNA) has emerged as a novel functional player transcribed from the genome. Here, we describe a novel lncRNA POU6F2-AS2 specifically expressed in OSCC. POU6F2-AS2 is involved in the DNA damage response and regulates cells survival after ionizing radiation. POU6F2-AS2 interacts with Ybx1 protein and regulates its chromatin localization. Our current study represents the first description of an OSCC associated lncRNA that modulates DNA repair.

['Liu|Jing|J|', 'Sun|Xiangdong|X|', 'Zhu|Hongcheng|H|', 'Qin|Qin|Q|', 'Yang|Xi|X|', 'Sun|Xinchen|X|']

2016

27511931

Sugar-Sweetened Beverages Are the Main Sources of Added Sugar Intake in the Mexican Population.

BACKGROUND Sugar intake has been associated with an increased prevalence of obesity, other noncommunicable diseases, and dental caries. The WHO recommends that free sugars should be <10% of total energy intake (TEI) and that additional health benefits could be obtained with a reduction below 5% of TEI. OBJECTIVE The objective of this study was to estimate the total, intrinsic, and added sugar intake in the Mexican diet and to identify the food groups that are the main sources of these sugars. METHODS We used data from a national probabilistic survey [ENSANUT (National Health and Nutrition Survey) 2012], which represents 3 geographic regions and urban and rural areas. Dietary information was obtained by administering a 24-h recall questionnaire to 10,096 participants. Total sugar intake was estimated by using the National Institute of Public Health (INSP) food-composition table and an established method to estimate added sugars. RESULTS The mean intakes of total, intrinsic, and added sugars were 365, 127, and 238 kcal/d, respectively. Added sugars contributed 13% of TEI. Sugar-sweetened beverages (SSBs) were the main source of sugars, contributing 69% of added sugars. Food products high in saturated fat and/or added sugar (HSFAS) were the second main sources of added sugars, contributing 25% of added sugars. CONCLUSIONS The average intake of added sugars in the Mexican diet is higher than WHO recommendations, which may partly explain the high prevalence of obesity and diabetes in Mexico. Because SSBs and HSFAS contribute >94% of total added sugars, strategies to reduce their intake should be strengthened. This includes stronger food labels to warn the consumer about the content of added sugars in foods and beverages.

['Sánchez-Pimienta|Tania G|TG|0000-0002-7743-0047', 'Batis|Carolina|C|0000-0002-2823-6651', 'Lutter|Chessa K|CK|0000-0003-1601-4645', 'Rivera|Juan A|JA|0000-0003-2586-4908']

2016

33810053

The Jump Shot Performance in Youth Basketball: A Systematic Review.

BACKGROUND The basketball jump shot (JS) is consensually considered as a high-complexity specific motor skill, with a complex teaching and learning processes involved. The aim of this paper was to conduct a systematic review of the literature on the JS performance among youth basketball players. METHODS The data search was made according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in the Institute for Scientific Information (ISI) Web of Knowledge, PubMed, Scopus and Sportdiscus databases until March 2021. RESULTS The results suggest that JS performance of youth basketball players is influenced by (i) distance to the basket, (ii) fatigue, (iii) presence of a defender and (iv) visual information available. CONCLUSION This research emphasizes the crucial need for players and coaches to promote training situations matching the game reality to develop successful shooting performance of youth basketball players.

['França|Cíntia|C|0000-0001-8364-6832', 'Gomes|Beatriz B|BB|0000-0003-2885-7666', 'Gouveia|Élvio Rúbio|ÉR|0000-0003-0927-692X', 'Ihle|Andreas|A|', 'Coelho-E-Silva|Manuel J|MJ|0000-0003-4512-7331']

2021

22690066

Adjuvant treatment in biliary tract cancer: to treat or not to treat?

Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic management. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of adjuvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Well-designed multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase III trials may provide relevant information.

['Cereda|Stefano|S|', 'Belli|Carmen|C|', 'Reni|Michele|M|']

2012

25917080

Impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in older subjects.

UNLABELLED An inverse, dose-dependent relationship between retrograde shear rate and brachial artery endothelial function exists in young subjects. This relationship has not been investigated in older adults, who have been related to lower endothelial function, higher resting retrograde shear rate and higher risk of cardiovascular disease. AIM To investigate the impact of a step-wise increase in retrograde shear stress on flow-mediated dilation in older males in the upper and lower limbs. METHODS Fifteen older (68 ± 9 years) men reported to the laboratory 3 times. We examined brachial artery flow-mediated dilation before and after 30-min exposure to cuff inflation around the forearm at 0, 30 and 60 mmHg, to manipulate retrograde shear rate. Subsequently, the 30-min intervention was repeated in the superficial femoral artery. Order of testing (vessel and intervention) was randomised. RESULTS Increases in cuff pressure resulted in dose-dependent increases in retrograde shear in both the brachial and superficial femoral artery in older subjects. In both the brachial and the superficial femoral artery, no change in endothelial function in response to increased retrograde shear was observed in older males ('time' P = 0.274, 'cuff*time P = 0.791', 'cuff*artery*time P = 0.774'). CONCLUSION In contrast with young subjects, we found that acute elevation in retrograde shear rate does not impair endothelial function in older humans. This may suggest that subjects with a priori endothelial dysfunction are less responsive or requires a larger shear rate stimulus to alter endothelial function.

['Schreuder|Tim H A|TH|', 'Green|Daniel J|DJ|', 'Hopman|Maria T E|MT|', 'Thijssen|Dick H J|DH|']

2015

27602799

Body volume, body fatness, and metabolic syndrome.

Body volume by three-dimensional body scanning (3DBS) may be an alternative index for evaluating body fatness. The aim of this study was to evaluate the association of body volume with body fatness and metabolic syndrome. This study included 38 Korean women whose body volume was measured using 3DBS. We measured body fatness using dual-energy X-ray absorptiometry and computed tomography. Participants with metabolic syndrome were defined as having three or more of the following components: high blood pressure (≥130/85 mmHg), elevated fasting glucose (≥100 mg/dl), hypertriglyceridemia (≥150 mg/dl), low high-density lipoprotein-cholesterol (<50 mg/dl), and abdominal obesity measured by waist circumference ≥80 cm. Total body, trunk, lower trunk, and limb volumes were significantly correlated with body mass index, waist circumference, total fat mass, percentage body fat, and abdominal fat areas. After adjustment for age, current smoking, at-risk drinking, and physical inactivity, the odds ratios (95% confidence intervals) for metabolic syndrome associated with total body, trunk, lower trunk, and limb volume were 1.08 (1.01-1.16), 1.11 (1.01-1.22), 1.20 (1.01-1.43), and 1.31 (1.04-1.66), respectively. Body volume by 3DBS was significantly associated with body fatness and metabolic syndrome. 3DBS may be a useful tool for detecting and monitoring body fatness and metabolic syndrome.

['Oh|Eun Jung|EJ|', 'Choi|Jaekyung|J|', 'Kim|Seonah|S|', 'Ahn|Aleum|A|', 'Park|Chang Kyu|CK|']

2017

24681254

Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster.

4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of pesticides, plastic, rubber, flame retardants, and tire production. Although, several studies have reported the ovotoxicity of VCH, information on a possible involvement of oxidative stress in the toxicity of this occupational chemical is scarce. Hence, this study was carried out to investigate further possible mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days old were exposed to different concentrations of VCH (10 µM-1 mM) in the diet for 5 days. Subsequently, the survival and negative geotaxis assays and the quantification of reactive oxygen species (ROS) generation were determined. In addition, we evaluated RT-PCR expressions of selected oxidative stress and antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase). Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid dehydratase (δ-ALA-D), and acetylcholinesterase (AChE) activities were determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and ROS production, as well as inhibitions of GST, δ-ALA-D, and AChE activities (P<0.05). Our results suggest that the VCH mechanism of toxicity is associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant balance, and possible neurotoxic consequences due to decreased AChE activity, and impairments in negative geotaxic behavior. Thus, we conclude that D. melanogaster is a useful model for investigating the toxicity of VCH exposure, and here, we have provided further insights on the mechanism of VCH-induced toxicity.

['Olalekan Abolaji|Amos|A|', 'Paul Kamdem|Jean|J|', 'Henrique Lugokenski|Thiago|T|', 'Kalar Nascimento|Thallita|T|', 'Pansera Waczuk|Emily|E|', 'Olatunde Farombi|Ebenezer|E|', 'da Silva Loreto|Élgion Lúcio|ÉL|', 'Teixeira Rocha|João Batista|JB|']

2014

33717807

Resection of Foramen Magnum Meningioma through Modified Far Lateral Approach: Surgical Principles and Technical Nuances.

Objectives  Safe maximal resection is the basic principle of cranial base surgery and the grade of resection is an important factor influencing the prognostic outcome. This operative video highlights the surgical principles and technical nuances in the microsurgical resection of foramen magnum meningioma (FMM). Case Description  The surgery was performed in a 45-year-old lady who presented with hoarseness of voice and spastic quadriparesis (grade 4/5). On imaging, FMM with mass effect on brainstem and spinal cord was identified. The tumor was gross totally resected through modified far lateral approach with minimal occipital condyle drilling. This video demonstrates the surgical techniques of tumor resection including early devascularization, operating in the arachnoid plane to dissect the neurovascular structures, piecemeal decompression, sharp dissection to separate tumor from lower cranial nerves (LCN), identifying the brainstem veins, and resecting the lesion from tumor-brainstem interface. Postoperatively, she had significant neurological improvement and the magnetic resonance imaging revealed excellent radiological outcome ( Figs. 1 and 2 ). Conclusion  The surgery of FMM is challenging due to the deep surgical corridor, critical location, close proximity with various neurovascular structures, firm consistency, and high vascularity of the tumor. The modified far lateral approach by preserving the occipital condyle may prevent the postoperative incidence of craniovertebral junction instability. The key operative principles to achieve the best surgical outcome include careful dissection along the arachnoid plane, gentle handling of cranial nerves, veins, and perforator vessels, avoidance of traction on brainstem and spinal cord, intraoperative neurophysiological monitoring, proper hemostasis, and meticulous dural closure. The link to the video can be found at: https://youtu.be/1qvAeUmNIUw .

['Narayan|Vinayak|V|', 'Jumah|Fareed|F|', 'Nanda|Anil|A|']

2021

32980881

An individual's propensity to disperse is dependent on the behavioral type of its peers but not its own behavioral type.

Intraspecific differences in the dispersal propensity of animals have been linked to interindividual variation in inherent tendencies (i.e., personality or behavioral type) that influence multiple aspects of an individual's behavior. Studies linking dispersal propensity and personality often (1) focus on defining behavioral tendencies with a single behavioral trait rather than multiple, (2) do not recognize that invertebrates may have behavioral tendencies that influence dispersal, and (3) do not consider how the behavioral type of other individuals affects the dispersal propensity of an individual. We documented multiple foraging behaviors of an aquatic predatory insect (Notonecta irrorata) and found that Notonecta individuals differ in their inherent behavioral tendency (i.e., degree of boldness); all foraging behaviors were correlated such that riskier behaviors were exhibited by the same individuals. We conducted an experiment in which we varied which behavioral types of Notonecta were placed in outdoor pools (passive, bold or both types present) and quantified how long it took for individuals to disperse. Passive and bold individuals had a similar propensity to disperse but the dispersal propensity of each behavioral type was influenced by the behavioral type of other conspecifics present in the pool. Our work reveals that (1) invertebrates have inherent behavioral tendencies that vary among individuals but these tendencies do not necessarily impact all of the behavior displayed by the individual (i.e., impact foraging but not dispersal) and (2) the inherent behavioral tendency of other individuals with which an animal co-occurs can affect habitat patch dynamics such as predation, competition, or colonization.

['Kitchen|Anthony J|AJ|', 'Chalcraft|David R|DR|http://orcid.org/0000-0002-2165-0948']

2020

32063927

Prevalence of Pre Diabetes and Type 2 Diabetes Mellitus among cement industry workers.

Objectives Occupational and environmental pollution have become an imperative jeopardy for developing devastating metabolic diseases. Limited animal model studies have examined the impact of exposure to cement dust on metabolic conditions. This study aimed to assess the prevalence of pre-diabetes and Type-2 diabetic mellitus (T2DM) among non-smoking cement mill workers. Methods This epidemiological cross sectional study was conducted in the "Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia" during the period Oct 2016 to June 2017. Initially 310 cement mill workers were interviewed; after the interview and clinical history taking, 186 non-smoking cement mill employees were finally recruited. The cement mill employees were exposed to cement dust-related pollution in a cement industry for eight hours a day for six days a week. The mean age was 36.56 ± 0.78 years, mean BMI was 25.70 ± 0.29 m/kg2, and mean period of employment in the cement industry was 82.77 ± 6.95 months. HbA1c was measured using the Dimension Xpand Plus Integrated Chemistry System (USA). Results The cement mill employees were divided into three groups: non-diabetics group, with glycated hemoglobin (HbA1c) <5.7%; pre-diabetics group, with HbA1c 5.7-6.4%; and diabetics group, with HbA1c >6.4%. Among the cement mill personnel, 79 (42.47%) were non-diabetics, 28 (15.05%) were pre-diabetics, and 79 (42.47%) were diabetics. The prevalence of pre-diabetes and T2DM among cement mill employees was considerably associated with the period of employment in the cement industry (p=0.032). Conclusions Exposure to cement dust was associated with an increased prevalence of pre- diabetes and T2DM among cement industry employees.

['Meo|Sultan Ayoub|SA|', 'Muneif|Yasser Abdullah Bin|YAB|', 'BenOmran|Nasser Abdullah|NA|', 'AlSadhan|Mohammad Abdullah|MA|', 'Hashem|Raed Fuad|RF|', 'Alobaisi|Abdullah Saud|AS|']

2020

31906364

Significantly Improved Electrical Properties of Crosslinked Polyethylene Modified by UV-Initiated Grafting MAH.

Direct current (DC) electrical performances of crosslinked polyethylene (XLPE) have been evidently improved by developing graft modification technique with ultraviolet (UV) photon-initiation. Maleic anhydride (MAH) molecules with characteristic cyclic anhydride were successfully grafted to polyethylene molecules under UV irradiation, which can be efficiently realized in industrial cable production. The complying laws of electrical current varying with electric field and the Weibull statistics of dielectric breakdown strength at altered temperature for cable operation were analyzed to study the underlying mechanism of improving electrical insulation performances. Compared with pure XLPE, the appreciably decreased electrical conductivity and enhanced breakdown strength were achieved in XLPE-graft-MAH. The critical electric fields of the electrical conduction altering from ohm conductance to trap-limited mechanism significantly decrease with the increased testing temperature, which, however, can be remarkably raised by grafting MAH. At elevated temperatures, the dominant carrier transport mechanism of pure XLPE alters from Poole-Frenkel effect to Schottky injection, while and XLPE-graft-MAH materials persist in the electrical conductance dominated by Poole-Frenkel effect. The polar group of grafted MAH renders deep traps for charge carriers in XLPE-graft-MAH, and accordingly elevate the charge injection barrier and reduce charge mobility, resulting in the suppression of DC electrical conductance and the remarkable amelioration of insulation strength. The well agreement of experimental results with the quantum mechanics calculations suggests a prospective strategy of UV initiation for polar-molecule-grafting modification in the development of high-voltage DC cable materials.

['Zhao|Xin-Dong|XD|', 'Zhao|Hong|H|', 'Sun|Wei-Feng|WF|']

2020

32645425

Gastrointestinal diseases and their impact on drug solubility: Celiac disease.

The aim of this study was to develop an in vitro tool for predicting drug solubility and dissolution in intestinal fluids of patients with Celiac disease (CED). Biorelevant media for patients with CED were developed based on published information and a Design of Experiment (DoE) approach. The CED biorelevant media were characterised according to their surface tension, osmolality, dynamic viscosity and buffer capacity. By performing solubility studies of six drugs with different physicochemical properties in CED media, we aimed to identify drugs at high risk of altered luminal solubility in CED patients. Identified differences in CED patients compared to healthy subjects were related to a higher concentration of bile salts, lecithin and cholesterol and included as factors in the DoE resulting in 8 CED biorelevant media. Differences in media properties were observed for the surface tension between biorelevant media based on CED patients and healthy subjects. In terms of solubility, only a minimal effect of CED on the solubility of the hydrophilic neutral compound azathioprine was observed. For neutral moderately lipophilic compounds (budesonide, celecoxib), a higher surfactant concentration resulted in most cases in a higher drug solubility, while it was specific to each drug whether this was mainly driven by bile salts or lecithin. In comparison, drug solubilisation of ionisable compounds with moderate to high lipophilicity was less impacted by CED differences. The developed biorelevant CED media serve as in vitro tool to identify the main media factors impacting on drug solubility.

['Effinger|Angela|A|', "O'Driscoll|Caitriona M|CM|", 'McAllister|Mark|M|', 'Fotaki|Nikoletta|N|']

2020

29078129

Age and the association of dementia-related pathology with trajectories of cognitive decline.

The association of dementia-related pathologies with cognition is hypothesized to decrease as age advances. We examined this in 413 persons without cognitive impairment at baseline who completed annual cognitive evaluations during a mean of 10.4 years. After death, neuropathologic examinations quantified beta amyloid plaque load, neurofibrillary tangles, and transactive response DNA-binding protein 43 pathology, and identified Lewy bodies, hippocampal sclerosis, and gross and microscopic cerebral infarcts. We tested whether age at death modified associations of these neuropathologies with the nonlinear trajectory of cognitive decline using mixed-effects change point models. The rate of global cognitive decline was gradual at first and then increased approximately 10-fold in the last 3 years of life. After adjustment for all other pathologic indices, tangle density, gross infarcts, Lewy bodies, and transactive response DNA-binding protein 43 were associated with global cognitive decline. However, the deleterious association of dementia-related pathologies with cognitive decline did not systematically vary by age. This suggests that the neuropathologic mechanisms underlying late-life cognitive decline do not substantially differ across the spectrum of age.

['Jansen|Willemijn J|WJ|', 'Wilson|Robert S|RS|', 'Visser|Pieter Jelle|PJ|', 'Nag|Sukriti|S|', 'Schneider|Julie A|JA|', 'James|Bryan D|BD|', 'Leurgans|Sue E|SE|', 'Capuano|Ana W|AW|', 'Bennett|David A|DA|', 'Boyle|Patricia A|PA|']

2018

32150938

Muscle Loss after Chemoradiotherapy as a Biomarker of Distant Failures in Locally Advanced Cervical Cancer.

This study aimed to evaluate whether computed tomography (CT)-based muscle measurement predicts distant failure in patients with locally advanced cervical cancer (LACC). Data from 278 patients with LACC who underwent chemoradiation therapy (CCRT) between 2004 and 2017 were analysed. Changes in the skeletal muscle index (SMI), skeletal muscle density, and total adipose tissue index during CCRT were calculated from CT images taken at the baseline and after CCRT. The predictive capability of CT-based muscle measurement for distant failure was evaluated using Cox proportional hazards regression, Harrell's concordance index (C-index), and time-dependent receiver operating characteristic curves. SMI loss ≥ 5% was independently associated with worse distant recurrence-free survival (DRFS) (HR: 6.31, 95% CI: 3.18-12.53; p < 0.001). The addition of muscle change to clinical models, including International Federation of Gynaecology and Obstetrics (FIGO) stage, lymph nodes, pathology, and squamous cell carcinoma-antigen, achieved higher C-indices (0.824 vs. 0.756; p < 0.001). Models including muscle change had superior C-indices than those including weight change (0.824 vs. 0.758; p < 0.001). The area under the curve for predicting 3-year DRFS was the highest for the muscle-loss model (0.802, muscle-loss model; 0.635, clinical model; and 0.646, weight-loss model). Our study demonstrated that muscle loss after CCRT was independently associated with worse DRFS and that integrating muscle loss into models including classical prognostic factors improved the prediction of distant failure.

['Lee|Jie|J|0000-0003-1445-2393', 'Lin|Jhen-Bin|JB|', 'Wu|Meng-Hao|MH|', 'Chang|Chih-Long|CL|0000-0003-3981-9366', 'Jan|Ya-Ting|YT|', 'Chen|Yu-Jen|YJ|']

2020

23806717

Same or different? ERP correlates of pretense and false belief reasoning in children.

Pretend play, emerging at about 18 months, and explicit false belief (FB) understanding, arising around 4 years, constitute two pivotal milestones in the development of a Theory of Mind since both involve the ability to separate real from non-real content. The developmental lag has evoked vivid discussion with respect to whether or not pretense (PT) involves a metarepresentational understanding similar to FB. However, in children PT and FB have not yet been contrasted on a neural level to reveal whether they are subserved by the same neurocognitive mechanism. Therefore, the present event-related potential (ERP) study compared PT to a FB and to a non-mental control condition in 6- to 8-year-old children. Results revealed distinct ERP components for PT and FB. PT elicited a parietal P2, which was assumed to reflect the detection of incongruence, and a negative frontal slow wave (290-600 ms), which was associated with the identification of the intention underlying the pretend behavior. In contrast, FB evoked the characteristic positive fronto-central late slow wave (290-920 ms) that is supposed to indicate metarepresentation. Further, the broad distribution of the anterior slow-wave patterns associated with PT and FB reasoning was assumed to reflect the ongoing structural development and neural specialization of the respective areas, indicating the developmental progress in conceptualizing the mental domain. Given the differences in latency, polarity, and topography, PT and FB seem to rely on distinct neural substrates in children. The early negative frontal slow wave indicates that for PT reasoning children may use simple mentalizing processes such as intention processing, whereas the late positive slow-wave shows that for FB children may engage in metarepresentational processing. Therefore, the present findings seem to substantiate theoretical accounts postulating simple mentalistic reasoning for PT in children.

['Kühn-Popp|N|N|', 'Sodian|B|B|', 'Sommer|M|M|', 'Döhnel|K|K|', 'Meinhardt|J|J|']

2013

30648798

What Are You Waiting For? Real-Time Integration of Cues for Fricatives Suggests Encapsulated Auditory Memory.

Speech unfolds over time, and the cues for even a single phoneme are rarely available simultaneously. Consequently, to recognize a single phoneme, listeners must integrate material over several hundred milliseconds. Prior work contrasts two accounts: (a) a memory buffer account in which listeners accumulate auditory information in memory and only access higher level representations (i.e., lexical representations) when sufficient information has arrived; and (b) an immediate integration scheme in which lexical representations can be partially activated on the basis of early cues and then updated when more information arises. These studies have uniformly shown evidence for immediate integration for a variety of phonetic distinctions. We attempted to extend this to fricatives, a class of speech sounds which requires not only temporal integration of asynchronous cues (the frication, followed by the formant transitions 150-350 ms later), but also integration across different frequency bands and compensation for contextual factors like coarticulation. Eye movements in the visual world paradigm showed clear evidence for a memory buffer. Results were replicated in five experiments, ruling out methodological factors and tying the release of the buffer to the onset of the vowel. These findings support a general auditory account for speech by suggesting that the acoustic nature of particular speech sounds may have large effects on how they are processed. It also has major implications for theories of auditory and speech perception by raising the possibility of an encapsulated memory buffer in early auditory processing.

['Galle|Marcus E|ME|', 'Klein-Packard|Jamie|J|', 'Schreiber|Kayleen|K|', 'McMurray|Bob|B|']

2019

33356792

Changing the Care Paradigm for Patients: Advanced Illness Beds Care Model.

BACKGROUND Over 90 million Americans suffer from advanced illness (AI) and spend their last days of life in critical care units receiving costly, unwanted, aggressive medical care. OBJECTIVE Evaluate the impact of a specialized care model in medical/surgical units for hospitalized geriatric patients and patients with complex care requirements where designated AI beds align care with patient's wishes/goals, minimize aggressive interventions, and influence efficient resource utilization. DESIGN US based multi-facility retrospective, longitudinal descriptive study of screened positive AI patients in AI Beds (N = 1,237) from 3 facilities from 2015 to 2017. RESULTS Patient outcomes included 60% referrals to AI beds from ICU, a decrease of 39-49% in average ICU LOS, a 23% reduction of AI bed patient expirations, 9.0% referrals to hospice, and projected cost savings of $4,361.66/patient, US dollars. CONCLUSION Allocating AI beds to deliver care to AI patients resulted in a decreased cost of care by reducing overall hospital LOS, mortality, and efficient use of both critical care and hospital resources.

['Rimar|Alexander|A|', 'Friedman|M Isabel|MI|https://orcid.org/0000-0002-7738-4079', 'Quinteros|Maria G|MG|', 'Gooch|Rebecca A|RA|', 'Masick|Kevin D|KD|', 'DaCosta|Nicholas|N|', 'Spooner|Rachael L|RL|']

2021

31185353

Bacterial community assemblages in sediments under high anthropogenic pressure at Ichkeul Lake/Bizerte Lagoon hydrological system, Tunisia.

Bacterial communities inhabiting sediments in coastal areas endure the effect of strong anthropogenic pressure characterized by the presence of multiple contaminants. Understanding the effect of pollutants on the organization of bacterial communities is of paramount importance in order to unravel bacterial assemblages colonizing specific ecological niches. Here, chemical and molecular approaches were combined to investigate the bacterial communities inhabiting the sediments of the Ichkeul Lake/Bizerte Lagoon, a hydrological system under anthropogenic pressure. Although the microbial community of the Ichkeul Lake sediment was different to that of the Bizerte Lagoon, common bacterial genera were identified suggesting a lake-lagoon continuum probably due to the hydrology of the system exchanging waters according to the season. These genera represent bacterial "generalists" maintaining probably general biogeochemical functions. Linear discriminant analysis effect size (LEfSe) showed significant differential abundance distribution of bacterial genera according to the habitat, the pollution type and level. Further, correlation analyses identified specific bacterial genera which abundance was linked with pesticides concentrations in the lake, while in the lagoon the abundance of specific bacterial genera was found linked with the concentrations of PAHs (Polycyclic aromatic hydrocarbons) and organic forms of Sn. As well, bacterial genera which abundance was not correlated with the concentrations of pollutants were identified in both lake and lagoon. These findings represent valuable information, pointing out specific bacterial genera associated with pollutants, which represent assets for developing bacterial tools for the implementation, the management, and monitoring of bioremediation processes to mitigate the effect of pollutants in aquatic ecosystems.

['Ben Salem|Fida|F|', 'Ben Said|Olfa|O|', 'Cravo-Laureau|Cristiana|C|', 'Mahmoudi|Ezzeddine|E|', 'Bru|Noëlle|N|', 'Monperrus|Mathilde|M|', 'Duran|Robert|R|']

2019

26655074

Effect of adjunctive application of epigallocatechin-3-gallate and ethanol-wet bonding on adhesive-dentin bonds.

OBJECTIVES To determine the effect of the combined use of epigallocatechin-3-gallate (EGCG) and ethanol-wet bonding (EWB) on resin-dentin bonds. METHODS Sixty molars were sectioned, polished, and randomly divided into six groups (n=10) according to the following pretreatments: group 1, water-wet bonding (WWB); group 2, WWB with 0.02% (w/v) EGCG; group 3, WWB with 0.1% EGCG; group 4, EWB; group 5, EWB with 0.02% EGCG; and group 6, EWB with 0.1% EGCG. An etch-and-rinse adhesive was then used, followed by the resin composites building. The microtensile bond strength (MTBS), failure modes and interfacial nanoleakage were separately determined after 24h water storage or 10,000 runs of thermocycling. RESULTS Both pretreatment method (P<0.05) and thermocycling (P<0.05) significantly influenced bond strength and nanoleakage. Irrespective of thermocycling, the 0.02% EGCG/ethanol (group 5) pretreated adhesive-dentin interfaces showed higher MTBS than the control group (P<0.05). Nanoleakage expression of all groups increased after thermocycling (P<0.05) except group 5. Adhesive failure was the main fracture pattern in all groups. CONCLUSION This study showed that pretreatment with 0.02% EGCG/ethanol solutions can effectively improve immediate bond strength and bond stability of etch-and-rinse adhesives on dentin. CLINICAL SIGNIFICANCE The adjunctive application of EGCG and EWB provides a new strategy for dentists to obtain the desired bond effectiveness during adhesive restoration in clinical practice.

['Yang|Hongye|H|', 'Guo|Jingmei|J|', 'Deng|Donglai|D|', 'Chen|Zhiyong|Z|', 'Huang|Cui|C|']

2016

29205779

The Graduating European Dentist-Domain IV: Dentistry in Society.

This position paper outlines the areas of competence and learning outcomes of "The Graduating European Dentist" that specifically relates to Dentistry in Society. In addition to treating individual patients, a Dentist must be able to focus on promoting health, monitoring interventions and implementing effective strategies of care at community and population levels. This necessarily involves understanding population demography and health trends, engaging with health policy and promoting health. A Dentist must also understand population demography and health trends, in the context of the healthcare system within which they work.

['Gallagher|J|J|', 'Field|J C|JC|']

2017

34820768

Flexible attention system: Appearance time of split attention changes in accordance with the task difficulty level.

Although it is often assumed that spatial attention exists in the form of a unitary focus, the split-attention hypothesis proposes that attention can be simultaneously divided into two spatially noncontiguous positions and that the space in between can be ignored. However, whether split attention occurs directly based on the generation of attentional benefit or whether it requires a gradual divide from a unitary focus over time has not been clarified. In the present study, by using two spatial salient cues to direct the attention allocation of participants, we aimed to investigate whether attention requires time to divide from a unitary focus and whether the appearance time of split attention varies when the task difficulty level increases between experiments. The results showed that attention required time to divide from a unitary focus, and the position between the two cued positions was not excluded by attention when the stimulus-onset asynchrony (SOA) was 60 ms. However, as the task difficulty increased between experiments, the appearance time of split attention was earlier. These findings suggest that the appearance time of split attention has a certain flexibility and can be changed according to the task requirement, thus implying that split attention and unitary attention present some common attention mechanisms and that a split or unitary mode can be flexibly selected for an attention system.

['Zu|Guangyao|G|', 'Sang|Hanbin|H|', 'Zhou|Heng|H|', 'Zhang|Fan|F|', 'Wu|Xiaogang|X|', 'Wang|Aijun|A|', 'Zhang|Ming|M|']

2021

28490500

The wisdom of crowds for visual search.

Decision-making accuracy typically increases through collective integration of people's judgments into group decisions, a phenomenon known as the wisdom of crowds. For simple perceptual laboratory tasks, classic signal detection theory specifies the upper limit for collective integration benefits obtained by weighted averaging of people's confidences, and simple majority voting can often approximate that limit. Life-critical perceptual decisions often involve searching large image data (e.g., medical, security, and aerial imagery), but the expected benefits and merits of using different pooling algorithms are unknown for such tasks. Here, we show that expected pooling benefits are significantly greater for visual search than for single-location perceptual tasks and the prediction given by classic signal detection theory. In addition, we show that simple majority voting obtains inferior accuracy benefits for visual search relative to averaging and weighted averaging of observers' confidences. Analysis of gaze behavior across observers suggests that the greater collective integration benefits for visual search arise from an interaction between the foveated properties of the human visual system (high foveal acuity and low peripheral acuity) and observers' nonexhaustive search patterns, and can be predicted by an extended signal detection theory framework with trial to trial sampling from a varying mixture of high and low target detectabilities across observers (SDT-MIX). These findings advance our theoretical understanding of how to predict and enhance the wisdom of crowds for real world search tasks and could apply more generally to any decision-making task for which the minority of group members with high expertise varies from decision to decision.

['Juni|Mordechai Z|MZ|', 'Eckstein|Miguel P|MP|']

2017

28250686

Prevalence of tuberculosis among children in North Sudan: Are we only seeing the tip of the iceberg?

INTRODUCTION Tuberculosis (TB) is a significant cause of morbidity and mortality among children. The vague symptoms, the uncertain diagnostic tests and lack of adequate awareness among families all contributed in masking the actual prevalence of the disease. The objective of this study was to describe the epidemiology of childhood TB in River Nile State (RNS), North Sudan. METHODS All registered cases of TB aged 15 years and below, at the 13 management units in RNS during 3 years, 2011-2013 were included. The records included epidemiological, clinical, and microbiological data. RESULTS Out of the 1221 total TB notified cases, children were 187 (15.3%); almost equally distributed across the 3 years of the study period. Males were 56.7%. Most of the cases (89.9%) were newly diagnosed; among them, pulmonary TB (PTB) constituted 61.5%. Sputum specimen was tested in 59.4% (111/187) of cases, and only 15.3% (17/111) of specimens were sputum smear positive for new cases. The cure rate was (76.5%), and the treatment success rate was (88.2%). The death rate was 6.1% among PTB cases and 5.6% among extra-pulmonary cases. All the 20 (10.7%) children tested for HIV were negative. CONCLUSION TB is under-reported in RNS and treatment outcomes are sub-optimal. Strategies to identify the active case-detection among children are recommended.

['Elmadhooun|Wadie M|WM|', 'Salah|Elmuntasir Taha|ET|', 'Noor|Sufian K|SK|', 'Bushara|Sarra O|SO|', 'Ahmed|Ekhlas O|EO|', 'Mustafa|Hamdan|H|', 'Sulaiman|Amel A|AA|', 'Ahmed|Mohamed H|MH|']

2017

27457683

Simulation-based mentalizing generates a "proxy" self-reference effect in memory.

The self-reference effect (SRE) in memory is thought to depend on specialized mechanisms that enhance memory for self-relevant information. We investigated whether these mechanisms can be engaged "by proxy" when we simulate other people, by asking participants to interact with two virtual partners: one similar and one dissimilar to self. Participants viewed pairs of objects and picked one for themselves, for their similar partner, or their dissimilar partner. A surprise memory test followed that required participants to identify which object of each pair was chosen, and for whom. Finally, participants were shown both partners' object pairs again, and asked to indicate their personal preference. Four key findings were observed. Overlap between participants' own choice and those made for their partner was significantly higher for the similar than the dissimilar partner, revealing participants' use of their own preferences to simulate the similar partner. Recollection of chosen objects was significantly higher for self than for both partners and, critically, was significantly higher for similar than dissimilar partners. Source confusion between self and the similar partner was also higher. These findings suggest that self-reference by proxy enhances memory for non-self-relevant material, and we consider the theoretical implications for functional interpretation of the SRE.

['Allan|Kevin|K|', 'Morson|Suzannah|S|', 'Dixon|Susan|S|', 'Martin|Douglas|D|', 'Cunningham|Sheila J|SJ|']

2017

27307491

SPATA2 links CYLD to the TNF-α receptor signaling complex and modulates the receptor signaling outcomes.

TNF-α is a key regulator of innate immune and proinflammatory responses. However, the composition of the TNF-α receptor-associated signaling complexes (TNF-RSC) and the architecture of the downstream signaling networks are incompletely understood. We employed quantitative mass spectrometry to demonstrate that TNF-α stimulation induces widespread protein phosphorylation and that the scope of phosphorylation expands in a temporal manner. TNF-α stimulation also induces rapid ubiquitylation of components of the TNF-RSC Temporal analysis of the TNF-RSC composition identified SPATA2 as a novel component of the TNF-RSC The predicted PUB domain in the N-terminus of SPATA2 interacts with the USP domain of CYLD, whereas the C-terminus of SPATA2 interacts with HOIP SPATA2 is required for recruitment of CYLD to the TNF-RSC Downregulation of SPATA2 augments transcriptional activation of NF-κB and inhibits TNF-α-induced necroptosis, pointing to an important function of SPATA2 in modulating the outcomes of TNF-α signaling. Taken together, our study draws a detailed map of TNF-α signaling, identifies SPATA2 as a novel component of TNF-α signaling, and provides a rich resource for further functional investigations.

['Wagner|Sebastian A|SA|', 'Satpathy|Shankha|S|', 'Beli|Petra|P|', 'Choudhary|Chunaram|C|0000-0002-9863-433X']

2016

25582599

The combination of thioxodihydroquinazolinones and platinum drugs reverses platinum resistance in tumor cells by inducing mitochondrial apoptosis independent of Bax and Bak.

The effective management of tumors resistant to platinum drugs-based anticancer therapies is a critical challenge in current clinical practices. The proapoptotic Bcl-2 family proteins Bax and Bak are essential for cisplatin-induced apoptosis. Unfortunately, Bax and its related upstream endogenous apoptotic signaling pathways are often dysregulated in cancer cells. Strategies that are able to bypass Bax- and Bak-dependent apoptotic pathways will thus provide opportunities to overcome platinum drug resistance. We have identified the thioxodihydroquinazolinone mdivi-1 as a member of a novel class of small molecules that are able to induce Bax- and Bak-independent mitochondrial outer membrane permeabilization when combined with cisplatin, thereby efficiently triggering apoptosis in platinum-resistant tumor cells. In the present structure activity relationship (SAR) study of a computationally selected library of mdivi-1 related small molecules, we established a pharmacophore model that can lead to the enhancement of platinum drug efficacy and Bax/Bak-independent mitochondrial apoptosis. Specifically, we found that a thiourea function is necessary but not sufficient for the synergism of this class of thioxodihydroquinazolinones with cisplatin. We were also able to identify more potent mdivi-1 analogs through this SAR study, which will guide future designs with the goal to develop novel combination regimens for the treatment of platinum- and multidrug-resistant tumors.

['Qian|Wei|W|', 'Salamoun|Joseph|J|', 'Wang|Jingnan|J|', 'Roginskaya|Vera|V|', 'Van Houten|Bennett|B|', 'Wipf|Peter|P|']

2015

23633111

Travelers with cutaneous leishmaniasis cured without systemic therapy.

BACKGROUND Cutaneous leishmaniasis (CL) is a disfiguring but not life-threatening disease. Because antileishmanial drugs are potentially toxic, the World Health Organization (WHO) recommends simple wound care or local therapy as first-line treatment, followed or replaced by systemic therapy if local therapy fails or cannot be performed. METHODS To determine the feasibility and impact of the recommended approach, we analyzed the results of a centralized referral treatment program in 135 patients with parasitologically proven CL. RESULTS Infections involved 10 Leishmania species and were contracted in 29 different countries. Eighty-four of 135 patients (62%) were initially treated without systemic therapy. Of 109 patients with evaluable charts, 23 of 25 (92%) treated with simple wound care and 37 of 47 (79%) treated with local antileishmanial therapy were cured by days 42-60. In 37 patients with large or complex lesions, or preexisting morbidities, or who had not been cured with local therapy, the cure rate with systemic antileishmanial agents was 60%. Systemic adverse events were observed in 15 patients, all receiving systemic therapy. CONCLUSIONS In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

['Morizot|G|G|', 'Kendjo|E|E|', 'Mouri|O|O|', 'Thellier|M|M|', 'Pérignon|A|A|', 'Foulet|F|F|', 'Cordoliani|F|F|', 'Bourrat|E|E|', 'Laffitte|E|E|', 'Alcaraz|I|I|', 'Bodak|N|N|', 'Ravel|C|C|', 'Vray|M|M|', 'Grogl|M|M|', 'Mazier|D|D|', 'Caumes|E|E|', 'Lachaud|L|L|', 'Buffet|P A|PA|', '|||']

2013

23814689

Imaging of tuberculosis of the abdominal viscera: beyond the intestines.

There is an increasing incidence of both intra- and extra-thoracic manifestations of tuberculosis, in part due to the AIDS epidemic. Isolated tubercular involvement of the solid abdominal viscera is relatively unusual. Cross-sectional imaging with ultrasound, multidetector computed tomography (CT), and magnetic resonance imaging (MRI) plays an important role in the diagnosis and post treatment follow-up of tuberculosis. Specific imaging features of tuberculosis are frequently related to caseous necrosis, which is the hallmark of this disease. However, depending on the type of solid organ involvement, tubercular lesions can mimic a variety of neoplastic and nonneoplastic conditions. Often, cross-sectional imaging alone is insufficient in reaching a conclusive diagnosis, and image-guided tissue sampling is needed. In this article, we review the pathology and cross-sectional imaging features of tubercular involvement of solid abdominopelvic organs with a special emphasis on appropriate differential diagnoses.

['Tirumani|Sree Harsha|SH|', 'Ojili|Vijayanadh|V|', 'Gunabushanam|Gowthaman|G|', 'Shanbhogue|Alampady Krishna Prasad|AK|', 'Nagar|Arpit|A|', 'Fasih|Najla|N|', 'Chintapalli|Kedar N|KN|']

2013

29130416

Prevalence, incidence and associated factors of pressure ulcers in home palliative care patients: A retrospective chart review.

BACKGROUND Terminally ill patients are at high risk of pressure ulcers, which have a negative impact on quality of life. Data about pressure ulcers' prevalence, incidence and associated factors are largely insufficient. AIM To document the point prevalence at admission and the cumulative incidence of pressure ulcers in terminally ill patients admitted to an Italian home palliative care unit, and to analyse the patients' and caregivers' characteristics associated with their occurrence. DESIGN Retrospective chart review. SETTING/PARTICIPANTS Patients ( n = 574) with a life expectancy ⩽6 months admitted to a palliative home care service were included in this study. RESULTS The prevalence and incidence rates were 13.1% and 13.0%, respectively. The logistic regression models showed body mass index ( p < 0.001), Braden score at risk ( p < 0.001), Karnofsky Performance Scale index <30 ( p < 0.001), patients' female gender, patients' age >70 and >1 caregiver at home as the dichotomous variables predictors of presenting with a pressure ulcer at time of admission and during home palliative care. CONCLUSION The notable pressure ulcers' incidence and prevalence rates suggest the need to include this issue among the main outcomes to pursue during home palliative care. The accuracy of body mass index, Braden Scale and Karnofsky Performance Scale in predicting the pressure ulcers risk is confirmed. Therefore, they appear as essential tools, in combination with nurses' clinical judgment, for a structured approach to pressure ulcers prevention. Further research is needed to explore the home caregivers' characteristics and attitudes associated with the occurrence of pressure ulcers and the relations between their strategies for pressure ulcer prevention and gender-related patient's needs.

['Artico|Marco|M|', 'Dante|Angelo|A|', "D'Angelo|Daniela|D|", 'Lamarca|Luciano|L|', 'Mastroianni|Chiara|C|', 'Petitti|Tommasangelo|T|', 'Piredda|Michela|M|', 'De Marinis|Maria Grazia|MG|']

2018

33448932

Swedish Web Version of the Quality of Recovery Scale Adapted for Patients Undergoing Local Anesthesia and Peripheral Nerve Blockade (SwQoR-LA): Prospective Psychometric Evaluation Study.

BACKGROUND The frequency and timing of assessing patient symptoms and discomfort during postoperative recovery are goals. Therefore, real-time recovery evaluation has been suggested to identify specific deficits in patient recovery. OBJECTIVE This study aimed to psychometrically evaluate the Swedish Web Version of the Quality of Recovery (SwQoR) Scale adapted for patients undergoing local and peripheral nerve block (SwQoR-LA). METHODS This was a secondary analysis of a psychometric evaluation of 107 patients aged ≥18 years undergoing day surgery under local or peripheral nerve block anesthesia at 4 different day surgery departments in Sweden. The SwQoR-LA, available through a mobile app called Recovery Assessment by Phone Points (RAPP), was completed daily on postoperative days 1-7. RESULTS Some evidence of construct validity was supported, and discriminant validity was found in 7 of 8 items related to general anesthesia. The internal consistency was acceptable (.87-.89), and the split-half reliability was 0.80-0.86. Cohen d effect size was 0.98, and the percentage of change from baseline was 43.4%. No floor nor ceiling effects were found. CONCLUSIONS The SwQoR-LA is valid, reliable, responsive, and clinically feasible for digital real-time recovery assessment of patient recovery to identify specific deficits in patient recovery and detect those patients who might benefit from a timely intervention. TRIAL REGISTRATION ClinicalTrials.gov NCT02492191; https://clinicaltrials.gov/ct2/show/NCT02492191. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR2-10.1136/bmjopen-2015-009901.

['Nilsson|Ulrica|U|https://orcid.org/0000-0001-5403-4183', 'Dahlberg|Karuna|K|https://orcid.org/0000-0002-4170-6451', 'Jaensson|Maria|M|https://orcid.org/0000-0001-7574-6745']

2021

24101905

The effect of carbonic anhydrase IX on focal contacts during cell spreading and migration.

Carbonic anhydrase IX is a hypoxia-induced transmembrane enzyme linked with solid tumors. It catalyzes the reversible hydration of CO2 providing bicarbonate ions for intracellular neutralization and protons for extracellular acidosis, thereby supporting tumor cell survival and invasiveness. CA IX is the only human CA isoform containing the proteoglycan (PG) domain in its extracellular part. The PG domain appears to enhance the catalytic activity of CA IX and mediate its binding to the extracellular matrix. Moreover, manipulation of the CA IX level by siRNA or overexpression modulates cell adhesion pathway so that in the presence of CA IX, cells display an increased rate of adhesion and spreading. Here we show that deletion of the PG domain as well as treatment with the PG-binding monoclonal antibody M75 can impair this CA IX effect. Accordingly, CA IX-expressing cells show more prominent and elongated maturing paxillin-stained focal contacts (FC) than CA IX-negative controls, proving the role of CA IX in cell spreading. However, during active cell movement, CA IX is relocalized to lamellipodia and improves migration via its catalytic domain. Thus, we examined the influence of CA IX on FC turnover in these structures. While the lamellipodial regions lacking CA IX display dash-like adhesions, the CA IX-enriched neighboring regions exhibit dynamic dot-like FCs. These results suggest that CA IX can promote initial adhesion through its PG domain, but at the same time it facilitates formation of nascent adhesions at the leading edge of moving cells. Thereby it may allow for transmission of large forces and enhanced migration rate, presumably through catalytic activity and impact of pHe on FC dynamics. Thus, we provide the first evidence that CA IX protein localizes directly in focal adhesion (FA) structures and propose its functional relationship with the proteins involved in the regulation of FC turnover and maturation.

['Csaderova|Lucia|L|', 'Debreova|Michaela|M|', 'Radvak|Peter|P|', 'Stano|Matej|M|', 'Vrestiakova|Magdalena|M|', 'Kopacek|Juraj|J|', 'Pastorekova|Silvia|S|', 'Svastova|Eliska|E|']

2013

34595280

Organotypic Brain Cultures: A Framework for Studying CNS Infection by Neurotropic Viruses and Screening Antiviral Drugs.

According to the World Health Organization (WHO), at least 50% of emerging viruses endowed with pathogenicity in humans can infect the Central Nervous System (CNS) with induction of encephalitis and other neurologic diseases ( Taylor et al., 2001 ; Olival and Daszak, 2005). While neurological diseases are progressively documented, the underlying cellular and molecular mechanisms involved in virus infection and dissemination within the CNS are still poorly understood (Swanson and McGavern, 2015; Ludlow et al., 2016 ). For example, measles virus (MeV) can infect neural cells, and cause a persistent brain infections leading to lethal encephalitis from several months to years after primary infection with no available treatment (Reuter and Schneider-Schaulies, 2010; Laksono et al., 2016 ). The Organotypic Brain Culture (OBC) is a suitable model for the virology field to better understand the CNS infections. Indeed, it allows not only studying the infection and the dissemination of neurotropic viruses within the CNS but it could also serve as screening model of innovative antiviral strategies or molecules, such as our recently published studies about fusion inhibitory peptides and the HSP90 chaperone activity inhibitor, 17-DMAG ( Welsch et al., 2013 ; Bloyet et al., 2016 ). Based on our previous work, we propose here an optimized method to prepare OBC of hippocampi and cerebellums which are suitable for small rodent models based virus studies, including mice, rats as well as hamsters at a post-natal stage, between P6 to P10. We notably took into account the stress of the slice procedure on the tissue and the subsequent cellular reactions, which is essential to fully characterize the model prior to any use in infectious conditions. With this knowledge, we propose a protocol highlighting the requirements, including potential trouble shootings of the slicing parameters, to consider the variations we observed according to the structure and animal studied. This framework should facilitate the use of OBC for better conclusive studies of neurotropic viruses.

['Welsch|Jeremy Charles|JC|', 'Lionnet|Claire|C|', 'Terzian|Christophe|C|', 'Horvat|Branka|B|', 'Gerlier|Denis|D|', 'Mathieu|Cyrille|C|']

2017

25289194

Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development.

The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8-12 months and life expectancy is ∼5-6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0-1 month, 1-3 months, 3-6 months, 6 months-1 year and 1-4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have reached full weight. This study is the first to show the high abundance (100% in this study) of the supratrochlear foramen within the guinea pig humerus and the complete absence of a supracondylar foramen, which is different to many other species and may also affect potential fracture points and frequencies. Understanding bone morphology and growth is essential in not only understanding the requirements of the healthy guinea pig, but also necessary in order to investigate disease states.

['Witkowska|Agata|A|', 'Alibhai|Aziza|A|', 'Hughes|Chloe|C|', 'Price|Jennifer|J|', 'Klisch|Karl|K|', 'Sturrock|Craig J|CJ|', 'Rutland|Catrin S|CS|']

2014

33389272

Box-Behnken design optimisation of a green novel nanobio-based reagent for rapid visualisation of latent fingerprints on wet, non-porous substrates.

OBJECTIVE Optimisation of the green novel nanobio-based reagent (NBR) for rapid visualisation of groomed fingerprints on wet non-porous substrates using response surface methodology and assessment of its stability and sensitivity were attempted for forensic applications. RESULTS Scanning electron microscopy images demonstrated successful attachments of NBR onto the constituents of fingerprints on the substrates. The highest average quality of visualised fingerprints was attained at the optimum condition (100 mg of CRL; 75 mg of acid-functionalised multi-walled carbon nanotubes; 5 h of immobilisation). The NBR produced comparable average quality of fingerprints with the commercially available small particle reagent, even after 4 weeks of storage (without any preservatives) in both chilled and sultry conditions. The NBR was sensitive enough to visualise the increasingly weaker fingerprints, particularly on glass slides. CONCLUSION The optimised novel NBR could be the relatively greener option for visualising latent fingerprints on wet, non-porous substrates for forensic applications.

['Azman|Aida Rasyidah|AR|', 'Mahat|Naji Arafat|NA|http://orcid.org/0000-0002-0865-5461', 'Wahab|Roswanira Abdul|RA|', 'Ahmad|Wan Azlina|WA|', 'Puspanadan|Jive Kasturi|JK|', 'Huri|Mohamad Afiq Mohamed|MAM|', 'Kamaluddin|Mohammad Rahim|MR|', 'Ismail|Dzulkiflee|D|']

2021

24201044

Amelioration of diabetes-induced neurobehavioral and neurochemical changes by melatonin and nicotinamide: implication of oxidative stress-PARP pathway.

Diabetes associated hyperglycemia results in generation of reactive oxygen species which induces oxidative stress and initiate massive DNA damage leading to overactivation of poly (ADP-ribose) polymerase (PARP). In this study, we have elucidated the involvement of oxidative stress-PARP pathway using pharmacological interventions (melatonin, as an anti-oxidant and nicotinamide, as a PARP inhibitor) in diabetes-induced neurobehavioral and neurochemical alterations. Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of streptozotocin. Behavioral and cognitive deficits were assessed after 8weeks of diabetes induction using a functional observation battery, passive avoidance and rotarod test. Acetylcholinesterase activity was significantly decreased in hippocampus of diabetic rats as compared to control rats. Diabetic animals showed significant increase in malondialdehyde levels and reduction in NAD levels in hippocampus. Glutamate and GABA levels were also altered in hippocampus of the diabetic animals. Two week treatment with melatonin (3 and 10mg/kg) and nicotinamide (300 and 1000mg/kg) alone and in combination significantly improved the neurobehavioral parameters which were altered in diabetes. Neurotransmitter (glutamate and GABA) levels were improved by these interventions. Our results emphasize that simultaneous inhibition of oxidative stress-PARP overactivation cascade can be beneficial in treatment of diabetes associated CNS changes.

['Jangra|Ashok|A|', 'Datusalia|Ashok Kumar|AK|', 'Khandwe|Shriya|S|', 'Sharma|Shyam Sunder|SS|']

2013

21772948

Unilateral optic neuritis as a presentation of neurobrucellosis.

Neurobrucellosis manifesting as optic neuritis is a rare disease in childhood. We report a case of neurobrucellosis in a 11 year old girl leading to visual impairment and headache. Physical examination revealed mild oedema of right tibiotarsic joint and optic neuritis. Investigations showed CSF pleocytosis and a Brucella serum agglutination titer of 1/640. Complete reversal of the symptoms was observed after appropriate antibiotic treatment. To our knowledge only four cases of neurobrucellosis manifesting with visual impairment in childhood are previously reported in literature.

['Marques|Rita|R|', 'Martins|Cristina|C|', 'Machado|Inês|I|', 'Monteiro|José Paulo|JP|', 'Campos|Nuno|N|', 'Calhau|Paulo|P|']

2011

28446534

Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein Levels in Parathyroid Hyperplasia over Adenoma.

BACKGROUND/AIM To unveil the pathophysiology of primary hyperparathyroidism, molecular details of parathyroid hyperplasia and adenoma have to be revealed. Such details will provide the tools necessary for differentiation of these two look-alike diseases. Therefore, in the present study, a comparative proteomic study using postoperative tissue samples from the parathyroid adenoma and parathyroid hyperplasia patients was performed. MATERIALS AND METHODS Protein extracts were prepared from tissue samples (n=8 per group). Protein pools were created for each group and subjected to DIGE and conventional 2DE. Following image analysis, spots representing the differentially regulated proteins were excised from the and used for identification via MALDI-TOF/TOF analysis. RESULTS The identities of 40 differentially-expressed proteins were revealed. Fourteen of these proteins were over-expressed in the hyperplasia while 26 of them were over-expressed in the adenoma. CONCLUSION Most proteins found to be over-expressed in the hyperplasia samples were mitochondrial, underlying the importance of the mitochondrial activity as a potential biomarker for differentiation of parathyroid hyperplasia from adenoma.

['Akpinar|Gurler|G|', 'Kasap|Murat|M|', 'Canturk|Nuh Zafer|NZ|', 'Zulfigarova|Mehin|M|', 'Islek|Eylül Ece|EE|', 'Guler|Sertac Ata|SA|', 'Simsek|Turgay|T|', 'Canturk|Zeynep|Z|']

2017

24366915

Bioresorbable scaffolds: rationale, current status, challenges, and future.

Current generation of drug-eluting stents has significantly improved the outcomes of percutaneous coronary intervention by substantially reducing in-stent restenosis and stent thrombosis. However, a potential limitation of these stents is the permanent presence of a metallic foreign body within the artery, which may cause vascular inflammation, restenosis, thrombosis, and neoatherosclerosis. The permanent stents also indefinitely impair the physiological vasomotor function of the vessel and future potential of grafting the stented segment. Bioresorbable scaffolds (BRSs) have the potential to overcome these limitations as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage and restoring pulsatility, cyclical strain, physiological shear stress, and mechanotransduction. While a number of BRSs are under development, two devices with substantial clinical data have already received a Conformité Européenne marking. This review article presents the current status of these devices and evaluates the challenges that need to be overcome before BRSs can become the workhorse device in coronary intervention.

['Iqbal|Javaid|J|', 'Onuma|Yoshinobu|Y|', 'Ormiston|John|J|', 'Abizaid|Alexandre|A|', 'Waksman|Ron|R|', 'Serruys|Patrick|P|']

2014

24262187

Pathophysiology of language, speech and emotions in neurodegenerative disease.

Studying neurodegenerative diseases has greatly expanded our knowledge of language, speech and emotion as these diseases can affect areas not typically seen with stroke or tumor. Newer imaging techniques such as voxel based morphometry), fluorodeoxyglucose (F18) positron emission tomography and functional magnetic resonance imaging have allowed localization of these deficits and a greater understanding of the language network targeted by these progressive neurodegenerative illnesses. This review illustrates these important points by describing five syndromes, using clinical cases and then noting the anatomy, typical pathology, and proposed pathophysiology. The syndromes are Progressive Nonfluent Aphasia, Semantic Dementia, Logopenic Aphasia, Primary Progressive Apraxia of Speech and Dysprosody of Speech. Clinicians recognizing these syndromes using the associated clinico-anatomic patterns will lead to more accurate diagnosis and improved patient counseling and management. Further, patients may be included in appropriate clinical trials when their doctors are aware of the most likely pathology.

['Graff-Radford|Jonathan|J|', 'Jones|David T|DT|', 'Graff-Radford|Neill R|NR|']

2014

32862808

Vertical structure in chlorophyll profiles: influence on primary production in the Arctic Ocean.

Subsurface chlorophyll maximum (SCM) layers are prevalent throughout the Arctic Ocean under stratified conditions and are observed both in the wake of retreating sea ice and in thermally stratified waters. The importance of these layers on the overall productivity of Arctic pelagic ecosystems has been a source of debate. In this study, we consider the three principal factors that govern productivity within SCMs: the shape of the chlorophyll profile, the photophysiological characteristics of phytoplankton and the availability of light in the layer. Using the information on the biological and optical parameters describing the vertical structure of chlorophyll, phytoplankton absorption and photosynthesis-irradiance response curves, a spectrally resolved model of primary production is used to identify the set of conditions under which SCMs are important contributors to water-column productivity. Sensitivity analysis revealed systematic errors in the estimation of primary production when the vertical distribution of chlorophyll was not taken into account, with estimates of water-column production using a non-uniform profile being up to 97% higher than those computed using a uniform one. The relative errors were shown to be functions of the parameters describing the shape of the biomass profile and the light available at the SCM to support photosynthesis. Given that SCM productivity is believed to be largely supported by new nutrients, it is likely that the relative contribution of SCMs to new production would be significantly higher than that to gross primary production. We discuss the biogeochemical and ecological implications of these findings and the potential role of new ocean sensors and autonomous underwater vehicles in furthering the study of SCMs in such highly heterogeneous and remote marine ecosystems. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.

['Bouman|Heather A|HA|', 'Jackson|Thomas|T|', 'Sathyendranath|Shubha|S|', 'Platt|Trevor|T|']

2020

32944645

HSP70 promotes MLKL polymerization and necroptosis.

Mixed lineage kinase domain-like protein (MLKL) is the proposed executioner of necroptosis. Our recent findings identify a novel inhibitor necroptosis-blocking compound 1 (NBC1) which specifically conjugates to two cysteines of heat shock protein 70 (HSP70) to block its function. Importantly, HSP70 promotes MLKL polymerization to activate necroptosis.

['Johnston|Andrea N|AN|https://orcid.org/0000-0003-1082-1155', 'Wang|Zhigao|Z|https://orcid.org/0000-0002-6544-4302']

2020

26452117

The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation.

OBJECT The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans. METHODS The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1-Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler's method. RESULTS The authors identified the "classic" decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and the nondecussating dentatorubro tract. The left nd-DRTT encompasses 21.7% of the tracts and 24.9% of the volume of the left superior cerebellar peduncle, and the right nd-DRTT encompasses 20.2% of the tracts and 28.4% of the volume of the right superior cerebellar peduncle. CONCLUSIONS The connections of the DN with the RN and thalamus are bilateral, not ipsilateral only. This affords a potential anatomical substrate for bilateral limb motor effects originating in a single cerebellar hemisphere under physiological conditions, and for bilateral limb motor impairment in hemispheric cerebellar lesions such as ischemic stroke and hemorrhage, and after resection of hemispheric tumors and arteriovenous malformations. Furthermore, when a lesion is located on the course of the dentatorubrothalamic system, a careful preoperative tractographic analysis of the relationship of the DRTT, nd-DRTT, and the lesion should be performed in order to tailor the surgical approach properly and spare all bundles.

['Meola|Antonio|A|', 'Comert|Ayhan|A|', 'Yeh|Fang-Cheng|FC|', 'Sivakanthan|Sananthan|S|', 'Fernandez-Miranda|Juan C|JC|']

2016

33039270

Adverse Childhood Experiences and Suicidal Behaviors Among Youth: The Buffering Influence of Family Communication and School Connectedness.

PURPOSE The main objectives of this study were to determine (1) whether family communication and school connectedness offer protection against suicidal behaviors in the presence of adverse childhood experiences (ACEs; direct protective effect) and (2) whether family communication or school connectedness buffer the association between ACEs and suicidal behaviors (interacting protective effect) on the multiplicative and additive scales. METHODS Data were obtained from a western state's 2019 Youth Risk Behavior Survey that included 5,341 middle school and 4,980 high school participants. Generalized linear models were used to estimate whether family communication and school connectedness offered direct protection against suicidal behaviors or buffered the association between ACEs and suicidal behaviors using adjusted prevalence ratios and corresponding 95% confidence intervals. RESULTS Family communication and school connectedness offered direct protection against suicidal behaviors in the presence of ACEs (a 1-unit higher score was associated with a 32%-42% lower prevalence of suicidal behaviors for middle school youth and a 27%-39% lower prevalence of suicidal behaviors for high school youth). There was evidence that family communication and school connectedness buffered the association between ACEs and suicidal behaviors on the multiplicative scale. CONCLUSIONS The findings provide support for the development and implementation of interventions that build family communication and school connectedness to reduce suicidal behaviors. Furthermore, screening for trauma and suicidal behaviors is warranted.

['Lensch|Taylor|T|', 'Clements-Nolle|Kristen|K|', 'Oman|Roy F|RF|', 'Evans|William P|WP|', 'Lu|Minggen|M|', 'Yang|Wei|W|']

2021

31689901

Measuring Transformational Leadership in Establishing Nursing Care Excellence.

Transformational leadership (TL) is known to be essential to achieving Magnet® recognition, an internationally prestigious status for nursing care excellence. Since its inception in the 1980s, empirical studies have identified benefits of implementing the Magnet® Model involving improved patient care and nursing workforce outcomes. However, little is known about the leadership styles of nurse managers (NMs) working in a regional Australian context, which may hinder achieving Magnet® status. To close the knowledge gap, a self-administered survey was conducted to measure leadership styles of NMs at a large health organization comprising hospitals with a wide range of service profiles in regional Australia using a validated tool-the Multifactor Leadership Questionnaire (MLQ-6S). One-way of variance (ANOVA) was used to identify statistical significance between respondents' demographic characteristics (e.g., age, education, gender) and their MLQ-6S scores. Respondents (n = 78) reported their leadership styles as more transformational, compared to transactional or passive/avoidant leadership styles. The findings indicated that NMs' higher education (p = 0.02) and older age (p = 0.03) were associated with TL styles, whereas passive/avoidant leadership was generally reported by female (p = 0.04) and younger (p = 0.06) respondents. This study has identified differences in reported leadership styles among NMs, providing a unique organizational insight into developing strategies to improve NMs' TL, which could help to facilitate the implementation of the Magnet® framework. Healthcare organizations in similar settings could benefit from replicating this study to identify a dominant leadership style and customize strategies to improve TL.

['Moon|Sarah E|SE|', 'Van Dam|Pieter J|PJ|', 'Kitsos|Alex|A|']

2019

30993066

Accuracy of new and standard intraocular lens power calculations formulae in Saudi pediatric patients.

PURPOSE The purpose of this study is to compare the accuracy of new generation formulas to standard formulas for intraocular lens (IOL) power calculations in pediatric patients. SUBJECTS AND METHODS This retrospective case series compared the postoperative refractions to the predicted refractions after lensectomy and IOL implantation in pediatric patients. Four new generation formulas (Haigis, Holladay II, Olsen, and Barrett Universal II) were compared to four standard formulas (Holladay I, Hoffer Q, SRK/T, and SRKII) 4. The absolute prediction error (APE) was calculated as the absolute difference between the actual postoperative spherical equivalent and predicted spherical equivalent). The Friedman test was used to evaluate the difference between formulas. P < 0.05 was statistically significant. RESULTS The study sample was comprised 44 eyes from 29 patients (20 males and 9 females) with median age at surgery of 2.85 years (2.04-6.14 years). The Holladay I and II, Barrett Universal II, SRK/T, SRKII, Olsen, and Hoffer Q formulas had comparable median APE (MedAPE) of 1.32 D (0.51-2.11 D), 1.34 D (0.82-1.94 D), 1.28 D (0.73-1.85 D), 1.26 D (0.60-2.08 D), 1.16 D (0.54-1.16 D), 1.34 D (0.80-1.98 D), and 1.27 D (0.63-2.08 D), respectively (P = 1.0). The Haigis formula had the statistically highest MedAPE of 2.00 D (1.27-3.04 D) (P < 0.001). More than 70% of eyes were within ±2.0 D for the Holladay I and II, Barrett Universal II, SRK/T, SRKII, Olsen, and Hoffer Q formulas. Fifty percent of eyes were within ±2.0 D for the Haigis formula. CONCLUSION New generation IOL formulas do not outperform standard IOL formulas in predicting postoperative refraction for pediatric patients.

['An-Nakhli|Fouad Raja|FR|']

2019

25205162

Trichoderma species mediated differential tolerance against biotic stress of phytopathogens in Cicer arietinum L.

Trichoderma spp. have been reported to aid in imparting biotic as well as abiotic tolerance to plants. However, there are only few reports unfolding the differential ability of separate species of Trichoderma genera generally exploited for their biocontrol potential in this framework. A study was undertaken to evaluate the biocontrol potential of different Trichoderma species namely T. harzianum, T. asperellum, T. koningiopsis, T. longibrachiatum, and T. aureoviride as identified in the group of indigenous isolates from the agricultural soils of Eastern Uttar Pradesh, India. Their biocontrol potential against three major soilborne phytopathogens, i.e., Sclerotium rolfsii, Sclerotinia sclerotiorum, and Colletotrichum capsici was confirmed by dual culture plate technique. Efficient mycoparasitic ability was further assessed in all the isolates in relation to chitinase, β-1,3 glucanase, pectinase, lipase, amylase, and cellulase production while equally consistent results were obtained for their probable phosphate solubilization and indole acetic acid (IAA) production abilities. The selected isolates were further subjected to test their ability to promote plant growth, to reduce disease incidence and to tolerate biotic stress in terms of lignification pattern against S. rolfsii in chickpea plants. Among the identified Trichoderma species, excellent results were observed for T. harzianum and T. koningiopsis indicating better biocontrol potential of these species in the group and thus exhibiting perspective for their commercial exploitation.

['Saxena|Amrita|A|', 'Raghuwanshi|Richa|R|', 'Singh|Harikesh Bahadur|HB|']

2015

31573038

Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis.

BACKGROUND Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, is an important cause of miscarriage or adverse fetal effects, including neurological and ocular manifestations in humans. Current anti-Toxoplasma drugs have limited efficacy against toxoplasmosis and also have severe side effects. Therefore, novel efficacious drugs are urgently needed. Here, we identified metacytofilin (MCF) from a fungal Metarhizium species as a potential anti-Toxoplasma compound. METHODS Anti-Toxoplasma activities of MCF and its derivatives were evaluated in vitro and in vivo using nonpregnant and pregnant mice. To understand the mode of action of MCF, the RNA expression of host and parasite genes was investigated by RNAseq. RESULTS In vitro, MCF inhibited the viability of intracellular and extracellular T. gondii. Administering MCF intraperitoneally or orally to mice after infection with T. gondii tachyzoites increased mouse survival compared with the untreated animals. Remarkably, oral administration of MCF to pregnant mice prevented vertical transmission of the parasite. Interestingly, RNA sequencing of T. gondii-infected cells treated with MCF showed that MCF inhibited DNA replication and enhanced RNA degradation in the parasites. CONCLUSIONS With its potent anti-T. gondii activity, MCF is a strong candidate for future drug development against toxoplasmosis.

['Leesombun|Arpron|A|', 'Iijima|Masatomi|M|', 'Umeda|Kousuke|K|', 'Kondoh|Daisuke|D|', 'Pagmadulam|Baldorj|B|', 'Abdou|Ahmed M|AM|', 'Suzuki|Yutaka|Y|', 'Ohba|Shun-Ichi|SI|', 'Isshiki|Kunio|K|', 'Kimura|Tomoyuki|T|', 'Kubota|Yumiko|Y|', 'Sawa|Ryuichi|R|', 'Nihei|Coh-Ichi|CI|', 'Nishikawa|Yoshifumi|Y|']

2020

27649841

Energy restriction at young age, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk in the Netherlands Cohort Study.

The energy restriction (ER)-colorectal cancer (CRC) association is inconsistent in literature. To strengthen the biological plausibility of the ER-CRC association, we investigated whether genetic variation in the insulin-like growth factor (IGF) pathway, a putative underlying mechanism, modulated this association in the Netherlands Cohort Study. Participants completed a questionnaire (n = 120,852) and provided toenail clippings for DNA (∼75%) at baseline. Individuals living in a Western city during the Hunger Winter (1944-45) or Western rural versus non-Western area were exposed to (severe) ER at young age. Genotyping was performed for 3,768 subcohort members and 2,580 CRC cases (case-cohort with 16.3 years follow-up). Cox hazard ratios for CRC were estimated across combined categories of ER and a genetic sum score of unfavorable alleles based on 18 single nucleotide polymorphisms in IGF-related genes and ER and an IGF1 19-CA repeat polymorphism. The reference included ER exposed individuals, so that increased hazard ratios were expected in higher combined categories for calculating relative excess risks due to interaction (additive interactions). Wald tests for multiplicative interactions were also performed. Multiplicative and additive interactions were nonsignificant. Combined ER-genetic sum score categories showed increasing CRC risks in men, but confidence intervals were wide. Women carrying two variant IGF1 19-CA repeat alleles versus those carrying two wild type IGF1 19-CA repeat alleles were at an ∼50% decreased CRC risk, irrespective of ER exposure. In conclusion, data indicate that the IGF pathway might be involved in the ER-CRC association in men, but not women, although interactions were nonsignificant, hampering definite conclusions.

['Simons|Colinda C J M|CC|', 'Schouten|Leo J|LJ|', 'Godschalk|Roger W|RW|', 'van Engeland|Manon|M|', 'van den Brandt|Piet A|PA|', 'van Schooten|Frederik J|FJ|', 'Weijenberg|Matty P|MP|']

2017

31621517

Molecular surveillance of antimicrobial resistance and transmission pattern of Mycobacterium leprae in Chinese leprosy patients.

Reports on antimicrobial resistance (AMR) of Mycobacterium leprae, relationship with bacteriological index (BI), and transmission in China are limited. We investigated the emergence of AMR mutations, the relationship between BI and AMR in complete, moderate and lack of BI decline cases, and molecular epidemiological features of AMR cases by enrolling 290 leprosy cases from four endemic provinces. Seven (2.41%), one (0.34%), five (1.72%), one (0.34%), and one (0.34%) strains had single mutations in folP1, rpoC, gyrA, gyrB, and 23S rRNA, respectively. Double mutations in folP1 and gyrA, rpoB and gyrA, and gyrA and 23S rRNA were observed in one (0.34%) strain each. Mutated strains occurred in three out of 81 (95% CI-0.005-0.079, p = 0.083) cases with complete BI decline, in seven out of 103 (95% CI 0.018-0.117, p = 0.008) cases with moderate BI decline, and in four out of 34 (95% CI 0.003-0.231, p = 0.044) cases with lack of BI decline. Most of these mutated strains were geographically separated and diverged genotypically. AMR mutations may not be the main cause of the lack of BI decline. The low transmission of AMR strains at the county level indicates an ongoing transmission at close contact levels.

['Chokkakula|Santosh|S|https://orcid.org/0000-0002-1961-4454', 'Chen|Zhiming|Z|https://orcid.org/0000-0001-5794-8968', 'Wang|Le|L|https://orcid.org/0000-0002-9673-3879', 'Jiang|Haiqin|H|https://orcid.org/0000-0002-4924-0465', 'Chen|Yanqing|Y|https://orcid.org/0000-0003-3092-1823', 'Shi|Ying|Y|https://orcid.org/0000-0002-0301-6791', 'Zhang|Wenyue|W|https://orcid.org/0000-0001-7054-8037', 'Gao|Wei|W|https://orcid.org/0000-0002-4246-8440', 'Yang|Jun|J|https://orcid.org/0000-0003-2965-2080', 'Li|Jinlan|J|https://orcid.org/0000-0002-0376-938X', 'Li|Xiong|X|https://orcid.org/0000-0001-9374-9456', 'Shui|Tiejun|T|https://orcid.org/0000-0002-2224-0545', 'He|Jun|J|https://orcid.org/0000-0002-5188-0218', 'Shen|Limei|L|https://orcid.org/0000-0002-7449-423X', 'Liu|Jie|J|https://orcid.org/0000-0001-9999-7274', 'Wang|De||https://orcid.org/0000-0002-3737-6621', 'Wang|Hao|H|https://orcid.org/0000-0002-1045-4642', 'Chen|Huan|H|https://orcid.org/0000-0001-9447-5151', 'Kuang|Yanfei|Y|https://orcid.org/0000-0003-4988-329X', 'Li|Bin|B|https://orcid.org/0000-0001-9389-7539', 'Chen|Ziyi|Z|https://orcid.org/0000-0001-9870-4361', 'Wu|Aiping|A|https://orcid.org/0000-0002-2960-9341', 'Yu|Meiwen|M|https://orcid.org/0000-0001-8000-6987', 'Yan|Liangbin|L|https://orcid.org/0000-0001-8169-9922', 'Suryadevara|Naveen Chandra|NC|https://orcid.org/0000-0003-2571-1290', 'Vissa|Varalakshmi|V|https://orcid.org/0000-0002-8994-3819', 'Liu|Weida|W|https://orcid.org/0000-0003-1936-3736', 'Wang|Hongsheng|H|https://orcid.org/0000-0001-5725-5053']

2019

33588359

The clinical impact and safety profile of high-dose intra-arterial verapamil treatment for cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

BACKGROUND Cerebral vasospasm (CVS) leads to delayed cerebral ischemia (DCI) and cerebral infarction, a potential cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). The objective of this study was to evaluate the clinical efficacy and safety profile of high-dose IA verapamil for aSAH in a large series of patients. METHODS Between 2011-2019, a retrospective cohort of 188 consecutive patients presenting with aSAH were reviewed. High-dose IA verapamil (> 20 mg per vascular territory on each side) was intermittently used for appropriate patients to manage symptomatic CVS. Of the 188 patients reviewed, 86 were treated with high-dose IA verapamil. The clinical efficacy and safety profile of our ruptured aneurysm patient cohort were compared to historical literature controls. The primary endpoints studied included radiographic stroke corresponding to cerebral vasospasm, clinical outcome at discharge and subsequent follow-up, and overall functional status as defined by the modified Rankin scale (mRS). The safety profile of high dose IA verapamil was a secondary endpoint. RESULTS IA verapamil was delivered between 2-16 days after ictus (median post-bleed day 6) and 74 % of patients had documented clinical improvement after therapy, with 61.5 % achieving good functional outcomes (mRS < 2). 25.5 % of all patients had evidence of vasospasm-related DCI. 3 patients sustained transient hemodynamic changes after verapamil treatment and 10 patients developed post-procedural seizures successfully managed with intravenous lorazepam. CONCLUSION High-dose IA verapamil treatment is well-tolerated in the high-risk aneurysmal subarachnoid hemorrhage population that experience severe, symptomatic CVS with good functional outcomes at follow-up.

['Mao|Gordon|G|', 'Gigliotti|Michael J|MJ|', 'Esplin|Nathan|N|', 'Sexton|Kevin|K|']

2021

25638778

Prospective evaluation of follow-up in melanoma patients in Germany - results of a multicentre and longitudinal study.

BACKGROUND Patient numbers requiring long-term melanoma surveillance are constantly rising. Surveillance is costly and guideline recommendations vary substantially. METHODS In this German nationwide study, information on surveillance and treatment of patients diagnosed with melanoma and melanoma in situ (MMis) between April and June 2008 was prospectively collected over four years. Additionally, patient self-report questionnaires were evaluated to assess anxiety, depression, health-related quality of life, socio-demographic information and use of disease specific health information sources at year 4 after primary diagnosis. RESULTS Complete data was available for 668 patients from 67 centres, of whom 96.0% were in regular melanoma surveillance. In year 3-4 of surveillance, only 55.6% of locoregionary metastases were detected during surveillance visits. Only 33.3% were self-detected by the patient even though 69.4% were documented as being clinically visible or palpable. Costs of 4year surveillance of 550 patients without tumour recurrence (stage I-IIC and MMis) accumulated to 228,155.75 €. Guideline-adherence for follow-up frequency, lymph node ultrasound, S100 serum level tests and diagnostic imaging recommendations was approximately 60% in year 3-4 of surveillance. Multivariate regression analysis showed that certain patient/tumour characteristics and regional differences were significantly associated with guideline deviations. The percentage of patients who exceeded published cut-off scores indicating clinically relevant symptoms of anxiety and depression were significantly increased. Patients frequently reported lack of psychosocial support and education but ascribed great importance to these. CONCLUSIONS We recommend further reduction of melanoma follow-up in low-risk melanoma patients and improvement of psycho-social support and patient education for all melanoma patients.

['Livingstone|E|E|', 'Krajewski|C|C|', 'Eigentler|T K|TK|', 'Windemuth-Kieselbach|C|C|', 'Benson|S|S|', 'Elsenbruch|S|S|', 'Hauschild|A|A|', 'Rompel|R|R|', 'Meiss|F|F|', 'Mauerer|A|A|', 'Kähler|K C|KC|', 'Dippel|E|E|', 'Möllenhoff|K|K|', 'Kilian|K|K|', 'Mohr|P|P|', 'Utikal|J|J|', 'Schadendorf|D|D|']

2015

29179741

Dietary energy drives the dynamic response of bovine rumen viral communities.

BACKGROUND Rumen microbes play a greater role in host energy acquisition than that of gut-associated microbes in monogastric animals. Although genome-enabled advancements are providing access to the vast diversity of uncultivated microbes, our understanding of variables shaping rumen microbial communities is in its infancy. Viruses have been shown to impact microbial populations through a myriad of processes, including cell lysis and reprogramming of host metabolism. However, little is known about the processes shaping the distribution of rumen viruses or how viruses may modulate microbial-driven processes in the rumen. To this end, we investigated how rumen bacterial and viral community structure and function responded in five steers fed four randomized dietary treatments in a crossover design. RESULTS Total digestible nutrients (TDN), a measure of dietary energy, best explained the variation in bacterial and viral communities. Additional ecological drivers of viral communities included dietary zinc content and microbial functional diversity. Using partial least squares regression, we demonstrate significant associations between the abundances of 267 viral populations and variables driving the variation in rumen viral communities. While rumen viruses were dynamic, 14 near ubiquitous viral populations were identified, suggesting the presence of a core rumen virome largely comprised of novel viruses. Moreover, analysis of virally encoded auxiliary metabolic genes (AMGs) indicates rumen viruses have glycosidic hydrolases to potentially augment the breakdown of complex carbohydrates to increase energy production. Other AMGs identified have a role in redirecting carbon to the pentose phosphate pathway and one carbon pools by folate to boost viral replication. CONCLUSIONS We demonstrate that rumen bacteria and viruses have differing responses and ecological drivers to dietary perturbation. Our results show that rumen viruses have implications for understanding the structuring of the previously identified core rumen microbiota and impacting microbial metabolism through a vast array of AMGs. AMGs in the rumen appear to have consequences for microbial metabolism that are largely in congruence with the current paradigm established in marine systems. This study provides a foundation for future hypotheses regarding the dynamics of viral-mediated processes in the rumen.

['Anderson|Christopher L|CL|', 'Sullivan|Matthew B|MB|', 'Fernando|Samodha C|SC|']

2017

33343750

Sagittal spinopelvic changes after posterior spinal fusion in adolescent idiopathic scoliosis.

Purpose This article examines if longer posterior spinal fusions with instrumentation (PSFI) into the lumbar spine (L3/4) alter spinopelvic parameters compared with selective fusions to T12/L1/L2 in adolescent idiopathic scoliosis (AIS) patients. Methods We analysed radiographs of 84 AIS patients, 58 (69%) females and 26 (31%) males, who underwent PSFI at an mean age of 15 years ± 2.5 years, range 10 years to 21 years, between 1st January 2007 and 31st December 2014. Radiographic parameters were measured pre- and post-operatively at most recent follow-up (range 2 years to 8.2 years): pelvic incidence (PI), lumbar lordosis (LL, L1-S1 and L4-S1), sagittal vertical alignment (SVA), scoliosis angle and proximal junctional kyphosis (PJK). PI-LL was calculated. Data was analysed using t-tests or Wilcoxon rank-sum tests. Results In total, 32 patients underwent a selective fusion with lowest instrumented vertebra (LIV) T12-L2, and 52 patients underwent a fusion with LIV L3-L4. In both groups, scoliosis angle was significantly corrected at follow-up (p < 0.005).Pre-operatively, both groups had similar LL (L1-S1) and PI-LL. Post-operatively, LL increased in the L3-4 fusion group (p < 0.005) but did not change in the selective fusion group (p = 0.116). This change in LL in the L3-4 fusion group affected the post-operative PI-LL (T12-L2 fusion -4.9° versus L3-4 fusion -13.6°, p = 0.002). No differences were seen in PI, SVA or LL L4-S1 between groups. Radiographic PJK occurred in seven of the L3-4 patients with and without PJK (noPJK -8.8° versus PJK -25.8°, p = 0.026). Conclusions In patients who underwent a fusion ending at L3 or L4, LL was increased. This altered the PI-LL relationship, and appeared to increase the risk of PJK. Level of evidence III.

['Burton|Denver A|DA|', 'Karkenny|Alexa J|AJ|', 'Schulz|Jacob F|JF|', 'Hanstein|Regina|R|', 'Gomez|Jaime A|JA|']

2020

33554149

Intranuclear immunostaining-based FACS protocol from embryonic cortical tissue.

Cell sorting can be used to purify cell populations for cell type-specific molecular probing. Fluorescence-activated cell sorting (FACS) coupled with high-throughput sequencing affords molecular signature identification for specific cell types. FACS has many challenges that limit comprehensive cell purification from the brain, leading to incomplete molecular characterization. Here, we present the intranuclear immunostaining-based FACS protocol with several modified steps, which allows optimized nuclei/cell sorting from mouse or human embryonic cortical tissue for distinct downstream molecular investigation of basal intermediate progenitors.

['Sakib|M Sadman|MS|', 'Sokpor|Godwin|G|', 'Nguyen|Huu Phuc|HP|', 'Fischer|Andre|A|', 'Tuoc|Tran|T|']

2021

29314447

Prognostic value of psychosocial factors for first and recurrent hospitalizations and mortality in heart failure patients: insights from the OPERA-HF study.

AIMS Psychosocial factors are rarely collected in studies investigating the prognosis of patients with heart failure (HF), and only time to first event is commonly reported. We investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for HF. METHODS AND RESULTS OPERA-HF is an observational study enrolling patients hospitalized for HF. In addition to clinical variables, psychosocial variables are recorded. Patients provide the information through questionnaires that include social information, depression and anxiety scores, and cognitive function. Kaplan-Meier, Cox regression and the Andersen-Gill model were used to identify predictors of first and recurrent events (readmissions or death). Of 671 patients (age 76 ± 15 years, 66% men) with 1-year follow-up, 291 had no subsequent event, 34 died without being readmitted, 346 had one or more unplanned readmissions, and 71 patients died after a first readmission. Increasing age, higher urea and creatinine, and the presence of co-morbidities (diabetes, history of myocardial infarction, chronic obstructive pulmonary disease) were all associated with increasing risk of first or recurrent events. Psychosocial variables independently associated with both the first and recurrent events were: presence of frailty, moderate-to-severe depression, and moderate-to-severe anxiety. Living alone and the presence of cognitive impairment were independently associated only with an increasing risk of recurrent events. CONCLUSION Psychosocial factors are strongly associated with unplanned recurrent readmissions or mortality following an admission to hospital for HF. Further research is needed to show whether recognition of these factors and support tailored to individual patients' needs will improve outcomes.

['Sokoreli|Ioanna|I|', 'Pauws|Steffen C|SC|', 'Steyerberg|Ewout W|EW|', 'de Vries|Gert-Jan|GJ|', 'Riistama|Jarno M|JM|', 'Tesanovic|Aleksandra|A|', 'Kazmi|Syed|S|', 'Pellicori|Pierpaolo|P|', 'Cleland|John G|JG|', 'Clark|Andrew L|AL|']

2018

30013306

A Supervised Learning Tool for Prostate Cancer Foci Detection and Aggressiveness Identification using Multiparametric magnetic resonance imaging/magnetic resonance spectroscopy imaging.

Prostate cancer is the most frequently diagnosed cancer in men in the United States. The current main methods for diagnosing prostate cancer include prostate-specific antigen test and transrectal biopsy. Prostate-specific antigen screening has been criticized for overdiagnosis and unnecessary treatment, and transrectal biopsy is an invasive procedure with low sensitivity for diagnosis. We provided a quantitative tool using supervised learning with multiparametric imaging to be able to accurately detect cancer foci and its aggressiveness. A total of 223 specimens from patients who received magnetic resonance imaging (MRI) and magnetic resonance spectroscopy imaging prior to the surgery were studied. Multiparametric imaging included extracting T2-map, apparent diffusion coefficient (ADC) using diffusion-weighted MRI, using dynamic contrast-enhanced MRI, and 3-dimensional-MR spectroscopy. A pathologist reviewed all 223 specimens and marked cancerous regions on each and graded them with Gleason scores, which served as the ground truth to validate our prediction model. In cancer aggressiveness prediction, the average area under the receiver operating characteristic curve (AUC) value was 0.73 with 95% confidence interval (0.72-0.74) and the average sensitivity and specificity were 0.72 (0.71-0.73) and 0.73 (0.71-0.75), respectively. For the cancer detection model, the average AUC value was 0.68 (0.66-0.70) and the average sensitivity and specificity were 0.73 (0.70-0.77) and 0.62 (0.60-0.68), respectively. Our method included capability to handle class imbalance using adaptive boosting with random undersampling. In addition, our method was noninvasive and allowed for nonsubjective disease characterization, which provided physician information to make personalized treatment decision.

['Kirlik|Gokhan|G|', 'Gullapalli|Rao|R|', "D'Souza|Warren|W|", 'Md Daud Iqbal|Gazi|G|', 'Naslund|Michael|M|', 'Wong|Jade|J|', 'Papadimitriou|John C||', 'Papadimitrou|John|J|', 'Roys|Steve|S|', 'Mistry|Nilesh|N|', 'Zhang|Hao|H|']

2018

27796494

The oblique occipital sinus: anatomical study using bone subtraction 3D CT venography.

BACKGROUND AND PURPOSE An occipital sinus draining into the sigmoid sinus has been termed the oblique occipital sinus (OOS). The frequency, anatomical features, patterns, and relationship with the transverse sinus of the oblique occipital sinus were analyzed in this study. MATERIALS AND METHODS The study included 1805 patients who underwent brain CT angiography during a 3-year period from 2013 to 2015. CT examinations were performed using a 64-slice MDCT system. RESULTS The OOS was identified in 41 patients (2.3%). There were many anatomical variations in the oblique occipital sinuses. A hypoplastic or aplastic TS was seen in 31 (75.6%) of the 41 patients with OOS. CONCLUSION Many anatomical variations in the oblique occipital sinus can be seen on CT venography. Some OOSs function as the main drainage route of the intracranial veins instead of the TS. Thus, careful examination is essential for preoperative evaluation in posterior fossa lesions.

['Shin|Hwa Seon|HS|', 'Choi|Dae Seob|DS|', 'Baek|Hye Jin|HJ|', 'Choi|Ho Cheol|HC|', 'Choi|Hye Young|HY|', 'Park|Mi Jung|MJ|', 'Kim|Ji Eun|JE|', 'Han|Jeong Yeol|JY|', 'Park|SungEun|S|']

2017

30711286

Technical considerations for generating somatosensation via cortical stimulation in a closed-loop sensory/motor brain-computer interface system in humans.

Somatosensory feedback is the next step in brain computer interface (BCI). Here, we compare three cortical stimulating array modalities for generating somatosensory percepts in BCI. We compared human subjects with either a 64-channel "mini"-electrocorticography grid (mECoG; 1.2-mm diameter exposed contacts with 3-mm spacing, N = 1) over the hand area of primary somatosensory cortex (S1), or a standard grid (sECoG; 1.5-mm diameter exposed contacts with 1-cm spacing, N = 1), to generate artificial somatosensation through direct electrical cortical stimulation. Finally, we reference data in the literature from a patient implanted with microelectrode arrays (MEA) placed in the S1 hand area. We compare stimulation results to assess coverage and specificity of the artificial percepts in the hand. Using the mECoG array, hand mapping revealed coverage of 41.7% of the hand area versus 100% for the sECoG array, and 18.8% for the MEA. On average, stimulation of a single electrode corresponded to sensation reported in 4.42 boxes (range 1-11 boxes) for the mECoG array, 19.11 boxes (range 4-48 boxes) for the sECoG grid, and 2.3 boxes (range 1-5 boxes) for the MEA. Sensation in any box, on average, corresponded to stimulation from 2.65 electrodes (range 1-5 electrodes) for the mECoG grid, 3.58 electrodes for the sECoG grid (range 2-4 electrodes), and 11.22 electrodes (range 2-17 electrodes) for the MEA. Based on these findings, we conclude that mECoG grids provide an excellent balance between spatial cortical coverage of the hand area of S1 and high-density resolution.

['Kramer|Daniel R|DR|', 'Kellis|Spencer|S|', 'Barbaro|Michael|M|', 'Salas|Michelle Armenta|MA|', 'Nune|George|G|', 'Liu|Charles Y|CY|', 'Andersen|Richard A|RA|', 'Lee|Brian|B|']

2019

30678041

Building Back Better: Local Health Department Engagement and Integration of Health Promotion into Hurricane Harvey Recovery Planning and Implementation.

Disaster recovery provides an opportunity to build healthier and more resilient communities. However, opportunities and challenges encountered by local health departments (LHDs) when integrating health considerations into recovery have yet to be explored. Following Hurricane Harvey, 17 local health and emergency management officials from 10 agencies in impacted Texas, USA jurisdictions were interviewed to describe the types and level of LHD engagement in disaster recovery planning and implementation and the extent to which communities leveraged recovery to build healthier, more resilient communities. Interviews were conducted between December 2017 and January 2018 and focused on if and how their communities were incorporating public health considerations into the visioning, planning, implementation, and assessment phases of disaster recovery. Using a combined inductive and deductive approach, we thematically analyzed interview notes and/or transcripts. LHDs reported varied levels of engagement and participation in activities to support their community's recovery. However, we found that LHDs rarely articulated or informed decision makers about the health impacts of recovery activities undertaken by other sectors. LHDs would benefit from additional resources, support, and technical assistance designed to facilitate working across sectors and building resilience during recovery.

['Kennedy|Mallory|M|', 'Gonick|Shannon|S|', 'Meischke|Hendrika|H|', 'Rios|Janelle|J|', 'Errett|Nicole A|NA|']

2019

30717469

Risk Factors for Same Pathogen Sepsis Readmission Following Hospitalization for Septic Shock.

(1) Background: Septic shock survivors frequently readmit because of subsequent infection. This study aimed to determine the rate and risk factors for same pathogen sepsis readmissions following hospitalization for septic shock. (2) Methods: We performed this retrospective study using data from a prospective septic shock registry at a single urban tertiary center. All the patients were treated with a protocol-driven resuscitation bundle therapy between 2011 and 2016. We collected data from adult (older than 18 years) patients readmitted with sepsis within 90 days of discharge following hospitalization for septic shock. (3) Results: Among 2062 septic shock patients, 690 were readmitted within 90 days of discharge. After excluding scheduled and non-sepsis admissions, we analyzed the data from 274 (13.3%) patients readmitted for sepsis. Most of the readmissions following septic shock were new infections rather than relapses of the initial infection. The culture-negative rate was 51.4% (141/274), while the same pathogen was isolated in 25% of cases (69/274). Multivariate analysis revealed that previous gram-negative bacteremia (OR, 9.902; 95% CI, 2.843⁻34.489), urinary tract infection (OR, 4.331; 95% CI, 1.723⁻10.882) and same site infection (OR, 6.894; 95% CI, 2.390⁻19.886) were significantly associated with readmission for sepsis caused by the same pathogen. (4) Conclusions: The sepsis readmission rate following the previous hospitalization for septic shock was 13.3% and one-quarter of those patients had the same pathogen isolated. Previous gram-negative bacteremia, and/or same site infection are predisposing factors for recurrent same-pathogen sepsis.

['Kim|June-Sung|JS|', 'Kim|Youn-Jung|YJ|', 'Ryoo|Seung Mok|SM|', 'Sohn|Chang Hwan|CH|', 'Ahn|Shin|S|', 'Seo|Dong Woo|DW|', 'Lim|Kyoung Soo|KS|', 'Kim|Won Young|WY|0000-0002-6904-5966']

2019

33044596

Cochlear implantation under local anesthesia and conscious sedation: an Italian experience.

PURPOSE To report our experience in performing cochlear implantation under local anesthesia in a group of patients who were deemed unfit for general anesthesia. METHODS A retrospective chart review was performed to analyze undesirable events and any other discomfort complained by patients during cochlear implantation. Analysis of patient's satisfaction was performed by means of a survey instrument. We have also compared the duration of surgery and hospitalization time with a control group that was implanted under general anesthesia. RESULT Twenty-one cochlear implantation in 20 patients were performed under local anesthesia. Age of patients ranged from 38 to 85 years. All interventions were successfully completed without any conversions to general anesthesia. Discomfort during surgery was reported in five cases: vertigo triggered by electrode insertion in two patients, pain during the round window approach in two patients and distress during the use of drill in one case; no patient experienced agitation. During the postoperative period, no complications or unpleasant experiences were reported. Only two patients stated that they would not perform cochlear implantation again under local anesthesia. Lower duration surgery and hospitalization time were found in the local anesthesia group. CONCLUSION Local anesthesia with conscious sedation is a safe and effective alternative for cochlear implant candidates considered unfit for general anesthesia. Fundamental for a successful procedure are preoperative counselling, accurate selection of the patients and constant intraoperative assistance. Unfeasibility of facial nerve monitoring and minor detrimental effect on training are the principal disadvantages in performing cochlear implantation under local anesthesia.

['Vincenti|Vincenzo|V|', 'Plantone|Francesca|F|', 'Ciavarro|Giovanni|G|http://orcid.org/0000-0001-8243-1653', 'Lusetti|Francesca|F|', 'Bartoli|Roberto|R|', 'Di Lella|Filippo|F|', 'Negri|Maurizio|M|', 'Fiorella|Maria Luisa|ML|', 'Quaranta|Nicola|N|']

2021

32295279

Foetal Immune Response Activation and High Replication Rate during Generation of Classical Swine Fever Congenital Infection.

Classical swine fever virus (CSFV) induces trans-placental transmission and congenital viral persistence; however, the available information is not updated. Three groups of sows were infected at mid-gestation with either a high, moderate or low virulence CSFV strains. Foetuses from sows infected with high or low virulence strain were obtained before delivery and piglets from sows infected with the moderate virulence strain were studied for 32 days after birth. The low virulence strain generated lower CSFV RNA load and the lowest proportion of trans-placental transmission. Severe lesions and mummifications were observed in foetuses infected with the high virulence strain. Sows infected with the moderately virulence strain showed stillbirths and mummifications, one of them delivered live piglets, all CSFV persistently infected. Efficient trans-placental transmission was detected in sows infected with the high and moderate virulence strain. The trans-placental transmission occurred before the onset of antibody response, which started at 14 days after infection in these sows and was influenced by replication efficacy of the infecting strain. Fast and solid immunity after sow vaccination is required for prevention of congenital viral persistence. An increase in the CD8+ T-cell subset and IFN-alpha response was found in viremic foetuses, or in those that showed higher viral replication in tissue, showing the CSFV recognition capacity by the foetal immune system after trans-placental infection.

['Bohórquez|José Alejandro|JA|0000-0002-6715-1757', 'Muñoz-González|Sara|S|', 'Pérez-Simó|Marta|M|', 'Muñoz|Iván|I|', 'Rosell|Rosa|R|', 'Coronado|Liani|L|', 'Domingo|Mariano|M|', 'Ganges|Llilianne|L|0000-0002-8644-3560']

2020

31648019

Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity.

Ocular hypertension due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM) is a major risk factor for glaucoma, a leading cause of irreversible blindness. However, the etiology of ocular hypertension remains unclear. Although autotaxin, a secreted lysophospholipase D and its catalytic product lysophosphatidic acid (LPA) have been shown to modulate AH drainage through TM, we do not have a complete understanding of their role and regulation in glaucoma patients, TM and AH outflow. This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1β and LPC treatment of TM cells also led to an increase in the levels of CTGF, fibronectin and collagen type 1 in an autotaxin dependent manner. Additionally, in perfused enucleated mouse eyes, autotaxin and LPC were noted to decrease, while inhibition of autotaxin was increased aqueous outflow through the TM. Taken together, these results provide additional evidence for dysregulation of the autotaxin-LPA axis in the AH of glaucoma patients, reveal molecular insights into the regulation of autotaxin expression in TM cells and the consequences of autotaxin inhibitors in suppressing the fibrogenic response and resistance to AH outflow through the TM.

['Ho|Leona T Y|LTY|', 'Osterwald|Anja|A|', 'Ruf|Iris|I|', 'Hunziker|Daniel|D|', 'Mattei|Patrizio|P|', 'Challa|Pratap|P|', 'Vann|Robin|R|', 'Ullmer|Christoph|C|', 'Rao|Ponugoti Vasanth|PV|']

2020

30167944

Long-term reported outcomes of transoral incisionless fundoplication: an 8-year cohort study.

BACKGROUND Transoral incisionless fundoplication (TIF) offers an endoscopic approach to the treatment of gastroesophageal reflux disease (GERD). Controlled trials have demonstrated the short-term efficacy of this procedure, but long-term follow-up studies are lacking. The objective of this study was to evaluate the long-term impact of TIF on disease-specific quality of life and antisecretory medication use. METHODS We performed retrospective cohort study of all patients undergoing TIF between 2007 and 2014 in a large academic medical center. Reflux symptoms and quality of life were assessed using the gastroesophageal reflux disease health-related quality of life (GERD-HRQL) questionnaire at baseline, short-term, and long-term follow-up. RESULTS Fifty-seven patients with a median age of 46 (37-59) years and an average BMI of 28.8 ± 4.9 kg/m2 underwent TIF during the study period. Sixty percent of the patients were female, and all were taking a PPI at least daily. At a median follow-up interval of 97 months, twelve patients had undergone subsequent laparoscopic antireflux surgery (LARS). Of those who had not, 23 had complete long-term follow-up data for analysis and were included in the study. Seventy-three percent reported daily acid-reducing medication use, and the median GERD-HRQL score was 10 (6-14) compared to 24 (15-28) at baseline (p < 0.01). Seventy-eight percent of these patients expressed satisfaction or neutral feelings about their GERD management. There were no significant differences in the baseline characteristics of patients who underwent LARS during the study period and those who did not. CONCLUSIONS This study demonstrates that TIF can produce durable improvements in disease-specific quality of life in some patients with symptomatic GERD. The majority of patients resumed daily PPI therapy during the study period, but with significantly improved GERD-HRQL scores compared to baseline and increased satisfaction with their medical condition.

['Chimukangara|Munyaradzi|M|0000-0001-8718-8111', 'Jalilvand|Anahita D|AD|', 'Melvin|W Scott|WS|', 'Perry|Kyle A|KA|']

2019

27026902

Impact response of a Timoshenko-type viscoelastic beam considering the extension of its middle surface.

In the present paper, the problem of low-velocity impact of an elastic sphere against a viscoelastic Timoshenko-type beam is studied considering the extension of its middle surface. The viscoelastic features of the beam out of the contact domain are governed by the standard linear solid model with derivatives of integer order, while within the contact domain the fractional derivative standard linear solid model is utilized, in so doing rheological constants of the material in both models are the same. However the presence of the additional parameter, i.e. fractional parameter which could vary from zero to unit, allows one to vary beam's viscosity, since the structure of the beam's material within this zone may be damaged, resulting in the decrease of the beam material viscosity in the contact zone. Consideration for transient waves (surfaces of strong discontinuity) propagating in the target out of the contact zone via the theory of discontinuities and determination of the desired values behind the surfaces of discontinuities upto the contact domain with the help of ray series, as well as the utilization of the Hertz theory in the contact zone allow one to obtain a set of two integro-differential equations, which govern the desired values, namely: the local bearing of the target and impactor's materials and the displacement of the beam within the contact domain.

['Rossikhin|Yury A|YA|', 'Shitikova|Marina V|MV|', 'Meza|Maria Guadalupe Estrada|MG|']

2016

29104215

Evaluation of PBS Treatment and PEI Coating Effects on Surface Morphology and Cellular Response of 3D-Printed Alginate Scaffolds.

Three-dimensional (3D) printing is an emerging technology for the fabrication of scaffolds to repair/replace damaged tissue/organs in tissue engineering. This paper presents our study on 3D printed alginate scaffolds treated with phosphate buffered saline (PBS) and polyethyleneimine (PEI) coating and their impacts on the surface morphology and cellular response of the printed scaffolds. In our study, sterile alginate was prepared by means of the freeze-drying method and then, used to prepare the hydrogel for 3D printing into calcium chloride, forming 3D scaffolds. Scaffolds were treated with PBS for a time period of two days and seven days, respectively, and PEI coating; then they were seeded with Schwann cells (RSC96) for the examination of cellular response (proliferation and differentiation). In addition, swelling and stiffness (Young's modulus) of the treated scaffolds was evaluated, while their surface morphology was assessed using scanning electron microscopy (SEM). SEM images revealed significant changes in scaffold surface morphology due to degradation caused by the PBS treatment over time. Our cell proliferation assessment over seven days showed that a two-day PBS treatment could be more effective than seven-day PBS treatment for improving cell attachment and elongation. While PEI coating of alginate scaffolds seemed to contribute to cell growth, Schwann cells stayed round on the surface of alginate over the period of cell culture. In conclusion, PBS-treatment may offer the potential to induce surface physical cues due to degradation of alginate, which could improve cell attachment post cell-seeding of 3D-printed alginate scaffolds.

['Mendoza García|María A|MA|', 'Izadifar|Mohammad|M|', 'Chen|Xiongbiao|X|']

2017

29988284

A Chromosome 4q25 Variant is Associated with Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Meta-Analysis.

Background Recent studies suggested that variants on chromosome loci 4q25, 1q21, and 16q22 were associated with atrial fibrillation recurrence after catheter ablation. In this study, we performed a systematic review and meta-analysis to explore the association between variants on chromosome loci 4q25, 1q21, and 16q22 and atrial fibrillation recurrence after catheter ablation. Methods We comprehensively searched the databases of MEDLINE and EMBASE from inception to January 2017. Included studies were published prospective or retrospective cohort and case control studies that compared the risk of atrial fibrillation recurrence after catheter ablation in AF patients with chromosome 4q25, 1q21, and 16q22 variants versus no variants. Single-nucleotide polymorphism rs1906617, rs2106261, rs7193343, rs2200733, rs10033464, rs13376333, and rs6843082 were included in this analysis. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals. Results Seven studies from January 2010 to June 2017 involving 3,322 atrial fibrillation patients were included in this meta-analysis. According to the pooled analysis, there was a strong independent association between chromosome 4q25 variant (rs2200733) and the risk of atrial fibrillation recurrence after catheter ablation (risk ratio 1.45 [95% confidence interval 1.15-1.83], P = 0.002). No association was found in other variants. Conclusion Our meta-analysis demonstrates a statistically significant increased risk of atrial fibrillation recurrence after catheter ablation in 4q25 variant (only in rs2200733) but not in 1q21 or 16q22 variants.

['Rattanawong|Pattara|P|', 'Chenbhanich|Jirat|J|', 'Vutthikraivit|Wasawat|W|', 'Chongsathidkiet|Pakawat|P|']

2018

27578787

The histone methyltransferase Setd7 promotes pancreatic progenitor identity.

Cell fate specification depends on transcriptional activation driven by lineage-specific transcription factors as well as changes in chromatin organization. To date, the interplay between transcription factors and chromatin modifiers during development is not well understood. We focus here on the initiation of the pancreatic program from multipotent endodermal progenitors. Transcription factors that play key roles in regulating pancreatic progenitor state have been identified, but the chromatin regulators that help to establish and maintain pancreatic fate are less well known. Using a comparative approach, we identify a crucial role for the histone methyltransferase Setd7 in establishing pancreatic cell identity. We show that Setd7 is expressed in the prospective pancreatic endoderm of Xenopus and mouse embryos prior to Pdx1 induction. Importantly, we demonstrate that setd7 is sufficient and required for pancreatic cell fate specification in Xenopus Functional and biochemical approaches in Xenopus and mouse endoderm support that Setd7 modulates methylation marks at pancreatic regulatory regions, possibly through interaction with the transcription factor Foxa2. Together, these results demonstrate that Setd7 acts as a central component of the transcription complex initiating the pancreatic program.

['Kofent|Julia|J|', 'Zhang|Juan|J|', 'Spagnoli|Francesca M|FM|0000-0001-7094-8188']

2016

31865459

Early renal dysfunction after temporary ileostomy construction.

PURPOSE Loop ileostomy is often used to prevent complications after colorectal surgery, but it has been reported to cause renal impairment. This study aimed to evaluate the changes in the renal function after ileostomy and to compare these with the renal function after low anterior resection without ileostomy (low-ANT). METHODS The subjects included 58 patients who underwent ileostomy construction and closure for rectal cancer. The estimated glomerular filtration rate (eGFR) was calculated at specific time points after the index surgery. In addition, we conducted a case-matched study on 147 patients who underwent low-ANT. RESULTS The eGFR was significantly lower at 1 month after ileostomy than at the time of ileostomy construction (78.8 vs. 84.0, p < 0.0001) and did not improve after ileostomy closure. The only risk factor for a reduced eGFR was preoperative chemotherapy or chemoradiotherapy. In the case-matched study, 36 patients were allocated for each of the two groups. The number of ileostomy patients with a reduced eGFR was significantly increased 1 month after the index surgery (p = 0.005). CONCLUSIONS The eGFR began to decrease at one month after ileostomy construction and did not improve after ileostomy closure.

['Yaegashi|Mizunori|M|', 'Otsuka|Koki|K|', 'Kimura|Toshimoto|T|', 'Matsuo|Teppei|T|', 'Fujii|Hitoshi|H|', 'Sato|Kei|K|', 'Takashimizu|Kiyoharu|K|', 'Hatanaka|Tomoki|T|', 'Yoshida|Toru|T|', 'Tono|Chihiro|C|', 'Sasaki|Akira|A|']

2020

33757297

Nanopore Sequencing Indicates That Tandem Amplification of Chromosome 20q11.21 in Human Pluripotent Stem Cells Is Driven by Break-Induced Replication.

Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. The appearance of culture-acquired CNVs in human pluripotent stem cells (PSCs) has prompted concerns for their use in regenerative medicine. A particular problem in PSC is the frequent occurrence of CNVs in the q11.21 region of chromosome 20. However, the exact mechanism of origin of this amplicon remains elusive due to the difficulty in delineating its sequence and breakpoints. Here, we have addressed this problem using long-read Nanopore sequencing of two examples of this CNV, present as duplication and as triplication. In both cases, the CNVs were arranged in a head-to-tail orientation, with microhomology sequences flanking or overlapping the proximal and distal breakpoints. These breakpoint signatures point to a mechanism of microhomology-mediated break-induced replication in CNV formation, with surrounding Alu sequences likely contributing to the instability of this genomic region.

['Halliwell|Jason A|JA|https://orcid.org/0000-0003-1070-1866', 'Baker|Duncan|D|', 'Judge|Kim|K|https://orcid.org/0000-0002-1811-428X', 'Quail|Michael A|MA|', 'Oliver|Karen|K|', 'Betteridge|Emma|E|https://orcid.org/0000-0002-6713-6346', 'Skelton|Jason|J|', 'Andrews|Peter W|PW|https://orcid.org/0000-0001-7215-4410', 'Barbaric|Ivana|I|']

2021

31827479

Combining Crop Growth Modeling and Statistical Genetic Modeling to Evaluate Phenotyping Strategies.

Genomic prediction of complex traits, say yield, benefits from including information on correlated component traits. Statistical criteria to decide which yield components to consider in the prediction model include the heritability of the component traits and their genetic correlation with yield. Not all component traits are easy to measure. Therefore, it may be attractive to include proxies to yield components, where these proxies are measured in (high-throughput) phenotyping platforms during the growing season. Using the Agricultural Production Systems Simulator (APSIM)-wheat cropping systems model, we simulated phenotypes for a wheat diversity panel segregating for a set of physiological parameters regulating phenology, biomass partitioning, and the ability to capture environmental resources. The distribution of the additive quantitative trait locus effects regulating the APSIM physiological parameters approximated the same distribution of quantitative trait locus effects on real phenotypic data for yield and heading date. We use the crop growth model APSIM-wheat to simulate phenotypes in three Australian environments with contrasting water deficit patterns. The APSIM output contained the dynamics of biomass and canopy cover, plus yield at the end of the growing season. Each water deficit pattern triggered different adaptive mechanisms and the impact of component traits differed between drought scenarios. We evaluated multiple phenotyping schedules by adding plot and measurement error to the dynamics of biomass and canopy cover. We used these trait dynamics to fit parametric models and P-splines to extract parameters with a larger heritability than the phenotypes at individual time points. We used those parameters in multi-trait prediction models for final yield. The combined use of crop growth models and multi-trait genomic prediction models provides a procedure to assess the efficiency of phenotyping strategies and compare methods to model trait dynamics. It also allows us to quantify the impact of yield components on yield prediction accuracy even in different environment types. In scenarios with mild or no water stress, yield prediction accuracy benefitted from including biomass and green canopy cover parameters. The advantage of the multi-trait model was smaller for the early-drought scenario, due to the reduced correlation between the secondary and the target trait. Therefore, multi-trait genomic prediction models for yield require scenario-specific correlated traits.

['Bustos-Korts|Daniela|D|', 'Boer|Martin P|MP|', 'Malosetti|Marcos|M|', 'Chapman|Scott|S|', 'Chenu|Karine|K|', 'Zheng|Bangyou|B|', 'van Eeuwijk|Fred A|FA|']

2019

31522687

Heterogeneity in transmission parameters of hookworm infection within the baseline data from the TUMIKIA study in Kenya.

BACKGROUND As many countries with endemic soil-transmitted helminth (STH) burdens achieve high coverage levels of mass drug administration (MDA) to treat school-aged and pre-school-aged children, understanding the detailed effects of MDA on the epidemiology of STH infections is desirable in formulating future policies for morbidity and/or transmission control. Prevalence and mean intensity of infection are characterized by heterogeneity across a region, leading to uncertainty in the impact of MDA strategies. In this paper, we analyze this heterogeneity in terms of factors that govern the transmission dynamics of the parasite in the host population. RESULTS Using data from the TUMIKIA study in Kenya (cluster STH prevalence range at baseline: 0-63%), we estimated these parameters and their variability across 120 population clusters in the study region, using a simple parasite transmission model and Gibbs-sampling Monte Carlo Markov chain techniques. We observed great heterogeneity in R0 values, with estimates ranging from 1.23 to 3.27, while k-values (which vary inversely with the degree of parasite aggregation within the human host population) range from 0.007 to 0.29 in a positive association with increasing prevalence. The main finding of this study is the increasing trend for greater parasite aggregation as prevalence declines to low levels, reflected in the low values of the negative binomial parameter k in clusters with low hookworm prevalence. Localized climatic and socioeconomic factors are investigated as potential drivers of these observed epidemiological patterns. CONCLUSIONS Our results show that lower prevalence is associated with higher degrees of aggregation and hence prevalence alone is not a good indicator of transmission intensity. As a consequence, approaches to MDA and monitoring and evaluation of community infection status may need to be adapted as transmission elimination is aimed for by targeted treatment approaches.

['Truscott|James E|JE|', 'Ower|Alison K|AK|', 'Werkman|Marleen|M|', 'Halliday|Katherine|K|', 'Oswald|William E|WE|', 'Gichuki|Paul M|PM|', 'Mcharo|Carlos|C|', 'Brooker|Simon|S|', 'Njenga|Sammy M|SM|', 'Mwandariwo|Charles|C|', 'Walson|Judd L|JL|', 'Pullan|Rachel|R|', 'Anderson|Roy|R|']

2019