Mesioangulation of mandibular second molars: A case report.

Abstract: This case report describes a simple alternative for treatment of mesioangulation of mandibular second molars. An 11-year-old girl was diagnosed with unilateral posterior crossbite, moderate incisor crowding and mesioangulation of the right mandibular second molar. The ectopic second molar was uprighted using a modified lingual arch with a distal hook and elastic chains. Orthodontic traction began after appliance installation and was activated once per month using 120 g of force. After six months, the right mandibular second molar was in an upright position. Orthodontic treatment continued with teeth levelling and alignment until acceptable occlusal and aesthetic results were achieved. Adequate stability was observed one year after debonding. The modified mandibular lingual arch with a distal hook is a simple and effective alternative to manage mesioangulation of mandibular second molars with minimum adverse effects and stable outcomes.

orthodontic
appliance
dentition
ectopic tooth eruption
permanent


Similarities and differences of X and Y chromosome homologous genes, SRY and SOX3, in regulating the renin-angiotensin system promoters.

Abstract: The renin-angiotensin system (RAS) is subject to sex-specific modulation by hormones and gene products. However, sex differences in the balance between the vasoconstrictor/proliferative ACE/ANG II/AT1 axis, and the vasodilator/antiproliferative ACE2/ANG-(1-7)/MAS axis are poorly known. Data in the rat have suggested the male-specific Y-chromosome gene Sry to contribute to balance between these two axes, but why the testis-determining gene has these functions remains unknown. A combination of in silico genetic/protein comparisons, functional luciferase assays for promoters of the human RAS, and RNA-Seq profiling in rat were used to address if regulation of Sry on the RAS is conserved in the homologous X-chromosome gene, Sox3. Both SRY and SOX3 upregulated the promoter of Angiotensinogen (AGT) and downregulated the promoters of ACE2, AT2, and MAS, likely through overlapping mechanisms. The regulation by both SRY and SOX3 on the MAS promoter indicates a cis regulation through multiple SOX binding sites. The Renin (REN) promoter is upregulated by SRY and downregulated by SOX3, likely through trans and cis mechanisms, respectively. Sry transcripts are found in all analyzed male rat tissues including the kidney, while Sox3 transcripts are found only in the brain and testis, suggesting that the primary tissue for renin production (kidney) can only be regulated by SRY and not SOX3. These results suggest that SRY regulation of the RAS is partially shared with its X-chromosome homolog SOX3, but SRY gained a sex-specific control in the kidney for the rate-limiting step of the RAS, potentially resulting in male-specific blood pressure regulation.

Araujo|Fabiano C|FC|
Milsted|Amy|A|
Watanabe|Ingrid K M|IK|
Del Puerto|Helen L|HL|
Santos|Robson A S|RA|
Lazar|Jozef|J|
Reis|Fernando M|FM|
Prokop|Jeremy W|JW|

D051876:Sex-Determining Region Y Protein

Sry
Sox3
sex differences
hypertension
renin angiotensin system


Naturopathy and Yoga as an Adjuvant for People Living With HIV/AIDS - A Case Series Report.

Abstract: Human Immunodeficiency Virus (HIV) is an infection that poses a great threat to both developed and developing countries. Health facilities offering complementary care, along with standard care, have been considered as a useful strategy to overcome the burden of HIV and promote quality and wellbeing among people living with HIV/AIDS (PLWHA). In this report, we make reference to seven participants diagnosed with HIV, who underwent naturopathy and yoga based lifestyle intervention (NYLI), for varying durations, at a sanatorium for PLWHA. The cases suggest that NYLI functions as an adjuvant therapy that complements standard care, improves adherence and promotes health-related outcomes in HIV affiliated clinical markers, such as haemoglobin, weight and CD4+ counts. However, further controlled trials are required to establish warranting evidence.

Naturopathy Yoga HIV AIDS Lifestyle CD4+


Nephrin Loss Can Be Used to Predict Remission and Long-term Renal Outcome in Patients With Minimal Change Disease.

Abstract:
Introduction
Minimal change disease is a common cause of nephrotic syndrome. In general, patients with minimal change disease respond to corticosteroids and have excellent long-term renal survival. However, some patients have less favorable outcome. These patients are often thought to have progressed to focal segmental glomerulosclerosis. We previously reported that a segmental loss of podocyte markers is present before the development of focal segmental glomerulosclerosis in a rat model. Here, we investigated whether loss of podocyte marker nephrin can serve as a biomarker for predicting poor outcome in patients with minimal change disease.

Methods
We obtained 47 kidney biopsy samples from patients diagnosed with minimal change disease and stained sections with periodic acid-Schiff and for nephrin. Nephrin loss was scored by 2 independent researchers who were blinded to clinical outcome. Clinical data were collected retrospectively, and nephrin loss was correlated with clinical follow-up data.

Results
Nephrin loss was present in 34% of the biopsy samples. During follow-up, patients with nephrin loss achieved remission less frequently (61%) compared to patients without (96%) (P = 0.002). Moreover, 5-year eGFR was lower in the patients with renal nephrin loss. The risk of eGFR decreasing to < 60 ml/min per 1.73m2 increased with each percentage of glomeruli with nephrin loss (hazard ratio = 1.044, 95% confidence interval = 1.02-1.07).

Conclusion
These results indicate that nephrin loss in patients with minimal change disease can help predict both remission and long-term renal outcome.

van de Lest|Nina A|NA|
Zandbergen|Malu|M|
IJpelaar|Daphne H T|DHT|
Wolterbeek|Ron|R|
Bruijn|Jan A|JA|
Bajema|Ingeborg M|IM|
Scharpfenecker|Marion|M|

nephrin
minimal change disease
nephrotic syndrome
focal segmental glomerulosclerosis
biomarker


Case of Vasovagal Syncope With Asystole Associated With Propofol Sedation.

Abstract: Few cases of bradycardic complications occurring under intravenous sedation have been reported. Here, we report a case of vasovagal syncope with asystole (7.2 seconds) associated with propofol sedation.


Effect of biofilm formation by clinical isolates of Helicobacter pylori on the efflux-mediated resistance to commonly used antibiotics.

Abstract:
AIM
To evaluate the role of biofilm formation on the resistance of Helicobacter pylori (H. pylori) to commonly prescribed antibiotics, the expression rates of resistance genes in biofilm-forming and planktonic cells were compared.

METHODS
A collection of 33 H. pylori isolates from children and adult patients with chronic infection were taken for the present study. The isolates were screened for biofilm formation ability, as well as for polymerase chain reaction (PCR) reaction with HP1165 and hp1165 efflux pump genes. Susceptibilities of the selected strains to antibiotic and differences between susceptibilities of planktonic and biofilm-forming cell populations were determined. Quantitative real-time PCR (qPCR) analysis was performed using 16S rRNA gene as a H. pylori-specific primer, and two efflux pumps-specific primers, hp1165 and hefA.

RESULTS
The strains were resistant to amoxicillin, metronidazole, and erythromycin, except for one strain, but they were all susceptible to tetracycline. Minimum bactericidal concentrations of antibiotics in the biofilm-forming cells were significantly higher than those of planktonic cells. qPCR demonstrated that the expression of efflux pump genes was significantly higher in the biofilm-forming cells as compared to the planktonic ones.

CONCLUSION
The present work demonstrated an association between H. pylori biofilm formation and decreased susceptibility to all the antibiotics tested. This decreased susceptibility to antibiotics was associated with enhanced functional activity of two efflux pumps: hp1165 and hefA.

D024901:Drug Resistance, Multiple, Bacterial

D060888:Real-Time Polymerase Chain Reaction

Biofilm
Helicobacter pylori
hp1165
Antibiotic resistance
Efflux genes
hefA


The CYCLOIDEA-RADIALIS module regulates petal shape and pigmentation, leading to bilateral corolla symmetry in Torenia fournieri (Linderniaceae).

Abstract: The diverse pigmentation patterns of flower corollas probably result from pollinator-mediated selection. Previous studies demonstrated that R2R3-MYB factors may have been recruited in the regulation of corolla pigmentation. However, how R2R3-MYBs became so diverse in their regulation of different pigmentation patterns remains unclear. Here, we studied a Lamiales species, Torenia fournieri, which has elaborate zygomorphic flowers with dorsal-ventral asymmetries in corolla pigmentation. We found recent gene duplication events in CYCLOIDEA-like (CYC-like) and RADIALIS-like (RAD-like) genes, and functionally analyzed three dorsal-specific expression factors: TfCYC1, TfCYC2, and TfRAD1. We found that the CYC-RAD module coordinates petal shape and corolla pigmentation, as ectopic expression of TfCYC2 or TfRAD1 disrupted the asymmetric corolla pigmentation pattern and produced strongly dorsalized flowers. Dorsal petal identity was lost when TfCYC2 was down-regulated or when TfRAD1 was knocked out. In T. fournieri, the diversified CYC and RAD genes have evolved regulatory loops, and TfCYC2 binds directly to the regulatory regions of an R2R3-MYB factor gene, TfMYB1, which might lead to its asymmetric expression and ultimately establish the asymmetric pigmentation pattern. These findings support the existence of a regulatory module that integrates dorsal-ventral patterning and asymmetric corolla pigmentation in T. fournieri.

Su|Shihao|S| Xiao|Wei|W| Guo|Wuxiu|W| Yao|Xinran|X| Xiao|Junqing|J| Ye|Ziqing|Z| Wang|Na|N| Jiao|Keyuan|K| Lei|Mengqi|M| Peng|Qincheng|Q| Hu|Xiaohe|X| Huang|Xia|X| Luo|Da|D|

D018506:Gene Expression Regulation, Plant

D012045:Regulatory Sequences, Nucleic Acid

Torenia fournieri
R2R3-MYB
Lamiales
dorsal-ventral asymmetry
corolla pigmentation pattern
CYC-like factor
RAD-like factor


Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease.

Abstract: Chagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited a higher frequency of hypoxia-inducible factor 1α and increased expression of its target genes/proteins. Nonclassical monocytes are expanded in patients' peripheral blood and represent an important source of NO. Monocytes entail CD8+ T cell surface nitration because both the frequency of nonclassical monocytes and that of NO-producing monocytes positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in in vitro-infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophages, diminishing the frequency of IL-1β- and NO-producing cells. In agreement, glycolysis inhibition reduced the percentage of TN+CD8+ T cells, improving their functionality. Altogether, these results clearly show that glycolysis governs oxidative stress on monocytes and modulates monocyte-T cell interplay in human chronic Chagas disease. Understanding the pathological immune mechanisms that sustain an inflammatory environment in human pathology is key to designing improved therapies.

Sanmarco|Liliana María|LM|
Eberhardt|Natalia|N|
Bergero|Gastón|G|
Quebrada Palacio|Luz Piedad|LP|
Adami|Pamela Martino|PM|
Visconti|Laura Marina|LM|
Minguez|Ángel Ramón|ÁR|
Hernández-Vasquez|Yolanda|Y|
Carrera Silva|Eugenio Antonio|EA|
Morelli|Laura|L|
Postan|Miriam|M|
Aoki|Maria Pilar|MP|

Monocytes
Cardiovascular disease
Glucose metabolism
Immunology
Metabolism


Ethanol extract of Kalopanax septemlobus leaf inhibits HepG2 human hepatocellular carcinoma cell proliferation via inducing cell cycle arrest at G1 phase.

Abstract:
OBJECTIVE
To investigate the effects of an ethanol extract of Kalopanax septemlobus (Thunb.) Koidz. leaf (EEKS) on cell proliferation in human hepatocellular carcinoma cells and its mechanisms of action.

METHODS
Cells were treated with EEKS and subsequently analyzed for cell proliferation and flow cytometry analysis. Expressions of cell cycle regulators were determined by reverse transcriptase polymerase chain reaction analysis and Western blotting, and activation of cyclin-associated kinases studied using kinase assays.

RESULTS
The EEKS suppressed cell proliferation in both HepG2 and Hep3B cells, but showed a more sensitive anti-proliferative activity in HepG2 cells. Flow cytometry analysis revealed an association between the growth inhibitory effect of EEKS and with G1 phase cell cycle arrest in HepG2 cells, along with the dephosphorylation of retinoblastoma protein (pRB) and enhanced binding of pRB with the E2F transcription factor family proteins. Treatment with EEKS also increased the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, without any noticeable changes in G1 cyclins and CDKs (except for a slight decrease in CDK4). Treatment of HepG2 cells with EEKS also increased the binding of p21 and p27 with CDK4 and CDK6, which was paralleled by a marked decrease in the cyclin D- and cyclin E-associated kinase activities.

CONCLUSIONS
Overall, our findings suggest that EEKS may be an effective treatment for liver cancer through suppression of cancer cell proliferation via G1 cell cycle arrest. Further studies are required to identify the active compounds in EEKS.

Park|Cheol|C|
Jeong|Ji-Suk|JS|
Jeong|Jin-Woo|JW|
Kim|Sung Ok|SO|
Kim|Yong-Joo|YJ|
Kim|Gi-Young|GY|
Hong|Su-Hyun|SH|
Choi|Yung Hyun|YH|

Kalopanax septemlobus
Hepatocellular carcinoma
pRB
CDK inhibitor
G(1) cell cycle arrest


An Early Report of the Use of a Modular Dual Mobility Articulation in Revision Acetabular Reconstruction.

Abstract:
BACKGROUND
Instability remains one of the main problems after revision hip surgery. The aim of this study was to review the clinical, radiological, and patient-reported outcomes with the use of modular dual-mobility articulation for revision acetabular reconstruction and investigate the risk of fretting corrosion by measuring serum trace metal ion levels.

METHODS
Sixty consecutive patients with a minimum of 24-month follow-up after the insertion of a modular dual-mobility (Stryker, Mahwah, NJ) cup at the time of revision hip surgery were identified. Follow-up included clinical and radiological patient review and functional outcome measures, and a subset of patients had their metal ion (cobalt and chromium) levels checked.

RESULTS
At the most recent follow-up, 5 patients had died, 3 patients have been revised because of ongoing instability, and 3 patients have had revision surgery due to infection. Overall functional outcome (mean Western Ontario and McMaster Universities Osteoarthritis Indexfunction 76, University of California, Los Angeles 5.6, mean Oxford 74.7, Short Form-12 physical 41.6/mental 53.3) and overall pain relief (mean Western Ontario and McMaster Universities Osteoarthritis Index pain score 78.3) scores were good. The mean satisfaction score was 78 of 100. The median serum trace metal chromium and cobalt levels at the most recent follow-up were 0.4 µg/L (range 0.1-6.1 µg/L) and 0.42 µg/L (range 0.21-9.42 µg/L), respectively. The survival with revision as the end point was 90%.

CONCLUSIONS
Dual-mobility cups with modularity represent an excellent option for the patient having revision hip surgery at high risk of instability. This series presents good patient-reported outcome measures and a low complication and revision rate.

Diamond|Owen J|OJ|
Konan|Sujith|S|
Greidanus|Nelson V|NV|
Garbuz|Donald S|DS|
Duncan|Clive P|CP|
Masri|Bassam S|BS|

modular dual mobility
instability
metal ion levels
functional outcome
acetabular component
revision hip arthroplasty


Use of Synthetic Hybrid Strains To Determine the Role of Replicon 3 in Virulence of the Burkholderia cepacia Complex.

Abstract: The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity with great biotechnological potential, but the utilization of these bacteria is limited by their opportunistic pathogenicity to humans. The third replicon of the Bcc, megaplasmid pC3 (0.5 to 1.4 Mb, previously chromosome 3), is important for various phenotypes, including virulence, antifungal, and proteolytic activities and the utilization of certain substrates. Approximately half of plasmid pC3 is well conserved throughout sequenced Bcc members, while the other half is not. To better locate the regions responsible for the key phenotypes, pC3 mutant derivatives of Burkholderia cenocepacia H111 carrying large deletions (up to 0.58 Mb) were constructed with the aid of the FLP-FRT (FRT, flippase recognition target) recombination system from Saccharomyces cerevisiae The conserved region was shown to confer near-full virulence in both Caenorhabditis elegans and Galleria mellonella infection models. Antifungal activity was unexpectedly independent of the part of pC3 bearing a previously identified antifungal gene cluster, while proteolytic activity was dependent on the nonconserved part of pC3, which encodes the ZmpA protease. To investigate to what degree pC3-encoded functions are dependent on chromosomally encoded functions, we transferred pC3 from Burkholderia cenocepacia K56-2 and Burkholderia lata 383 into other pC3-cured Bcc members. We found that although pC3 is highly important for virulence, it was the genetic background of the recipient that determined the pathogenicity level of the hybrid strain. Furthermore, we found that important phenotypes, such as antifungal activity, proteolytic activity, and some substrate utilization capabilities, can be transferred between Bcc members using pC3.IMPORTANCE The Burkholderia cepacia complex (Bcc) is a group of closely related bacteria with great biotechnological potential. Some strains produce potent antifungal compounds and can promote plant growth or degrade environmental pollutants. However, their agricultural potential is limited by their opportunistic pathogenicity, particularly for cystic fibrosis patients. Despite much study, their virulence remains poorly understood. The third replicon, pC3, which is present in all Bcc isolates and is important for pathogenicity, stress resistance, and the production of antifungal compounds, has recently been reclassified from a chromosome to a megaplasmid. In this study, we identified regions on pC3 important for virulence and antifungal activity and investigated the role of the chromosomal background for the function of pC3 by exchanging the megaplasmid between different Bcc members. Our results may open a new avenue for the construction of antifungal but nonpathogenic Burkholderia hybrids. Such strains may have great potential as biocontrol strains for protecting fungus-borne diseases of plant crops.

virulence
Burkholderia
Caenorhabditis elegans
antifungal agents
multiple replicons
synthetic biology


Quit Happens: A community clinic-based, multitiered smoking cessation intervention.

Abstract:
OBJECTIVES
To evaluate the "Quit Happens" program launched to reduce tobacco use in low-income populations in a federally qualified nonprofit health center with clinics in Washington and Idaho. Quit Happens was implemented in 2015 and involved a public health nurse, patient, provider, clinic, health system, and community components.

DESIGN AND SAMPLE
This smoking cessation program was assessed using a pre-post evaluation design. Nine clinics in a single system of federally qualified nonprofit health centers participated in this program.

INTERVENTION
The Quit Happens program was implemented across nine clinics in Washington and Idaho. A specialized public health nurse led the tobacco cessation training of all clinic staff and assisted with development of the smoking cessation program. The 5A model was used as the framework for the training.

MEASUREMENTS
The proportion of patients identifying as a current or former smoker was measured using data extracted from electronic health records.

RESULTS
Declines in patient reports of currently smoking were observed between 2016 and 2018. The percent of current smokers identified in electronic health records decreased 18.7% and percent of former smokers doubled.

CONCLUSION
This community-based tobacco cessation program had wide clinic and community support and self-reported smoking behavior declined over time. A public health nurse's leadership in offering training and program development around tobacco cessation to a local community organization can contribute to reductions in smoking rates.

Shishani|Kawkab|K|0000-0002-7792-6456
Graves|Janessa M|JM|0000-0002-7659-2634
McGowan|Paige|P|
Lockwood|William|W|
Nystrom|Melissa|M|
Barbosa-Leiker|Celestina|C|

public health nursing
tobacco cessation
public health programs


Acute Respiratory Failure With Hemoptysis in a Teenager Due to Cystic Echinococcosis.

Abstract: A previously healthy 14-year-old male presented with abrupt onset respiratory failure with hemoptysis and anaphylaxis. Imaging demonstrated a large, cystic lesion with bronchopleural fistula that was consistent with cystic echinococcosis. He underwent thoracotomy for cyst removal and bronchopleural fistula repair, then completed 3 months of albendazole therapy. He developed recurrence of a bronchopleural fistula 4 months after surgery which improved over time with conservative management. This case highlights pathognomonic imaging and pathology findings for cystic echinococcosis.

Blatz|Allison M|AM|0000-0003-2525-1212
Laycock|Katherine M|KM|
Kaur|Ishminder|I|
Swami|Sanjeev K|SK|

echinococcus
global health
hydatid cyst
parasitology
pediatrics


A Risk of Bias Assessment of Randomized Controlled Trials (RCTs) on Periodontal Regeneration Published in 2013.

Abstract:
OBJECTIVE
The objective of this assessment is to evaluate the degree of risk of bias in randomized controlled trials published in 2013 and focusing on periodontal regeneration.

METHODS
Three reviewers searched and selected the trials based on pre-defined inclusion criteria. Predictor variables [number of authors, primary objective of the study, biomaterial employed, follow-up time periods, split mouth study (yes/no), journal, year of publication, country, scale (single/multi-center) and nature of funding] were extracted and risk of bias assessment using Cochrane risk of bias tool were performed independently by the three reviewers.

RESULTS
Seventeen RCTs were included in this assessment. The risk of bias in RCTs published in 2013 with a focus in periodontal regeneration varied significantly with only in less than 30% of the included trials, the overall risk of bias was found to be low, while 41% of trials were designated to have a higher degree of bias. Specifically, when looking at the domains assessed, 70% of the included trials reported an accepted method of sequence generation, blinding (whenever possible), completeness of outcome data or avoided selective outcome reporting. Meanwhile, only 47% of the included trials reported some form of allocation concealment.

CONCLUSION
In this assessment, of the included 17 trials, slightly more than 40% of them had a high risk of bias, underscoring the importance of careful appraisal of trials before implementing the study interventions in clinical practice and the need for more detailed analyses.

Elangovan|Satheesh|S| Prakasam|Sivaraman|S| Gajendrareddy|Praveen|P| Allareddy|Veerasathpurush|V|

D016557:Guided Tissue Regeneration, Periodontal

D016032:Randomized Controlled Trials as Topic

Bias
Randomized controlled trial
Evidence based dentistry


Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial.

Abstract:
OBJECTIVE
The majority of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have low serum procalcitonin (PCT) values. The aim of this study was to determine whether these patients may benefit from antibiotic treatment.

METHODS
A total of 457 patients with AECOPD were screened; 194 patients with AECOPD and PCT <0.1 ng/ml were assigned randomly to an antibiotic group or a control group. In the per-protocol (PP) population, the antibiotic group subjects were required to have used antibiotics for at least 3 days, and the control group subjects were required not to have used antibiotics within the 10 days after admission. The intention-to-treat (ITT) population was defined as the patients who were randomized. The primary outcome was the treatment success rate on day 10 after admission. Secondary outcomes were symptoms assessed on a visual analog scale (VAS), length of hospitalization, mortality, exacerbation rate, and re-hospitalization within 30 days of follow-up (study registered at chictr.org.cn: ChiCTR-TRC-14004726).

RESULTS
95 patients in the antibiotic group and 96 patients in the control group completed the study. In the ITT population, the overall treatment success rate in the control group (95.8%) was similar to that in the antibiotic group (93.7%), with no significant difference (p=0.732). Five patients in the antibiotic group died, either in hospital or within 30 days of discharge. In the control group, two died within 30 days of discharge. Antibiotic use in the control group was 17.7% (17/96), and age ≥75 years was a predictive risk factor for requiring antibiotic therapy in the control group (odds ratio 4.055, 95% confidence interval 1.297-12.678; p=0.012). According to the PP analysis, the treatment success rate on day 10 after admission was 98.7% (78/79) in the control group and 93.7% (89/95) in the antibiotic group, also with no significant difference (p=0.193). No secondary outcome was significantly different between the two groups.

CONCLUSION
Antibiotic treatment is no better than placebo in AECOPD with a PCT level <0.1 ng/ml.

Wang|Jin-Xiang|JX| Zhang|Shu-Ming|SM| Li|Xiao-Hui|XH| Zhang|Yao|Y| Xu|Zhen-Yang|ZY| Cao|Bin|B|

D029424:Pulmonary Disease, Chronic Obstructive

Acute exacerbation
Chronic obstructive pulmonary disease
Procalcitonin
Antibiotics


Spatial masking: Development and testing of a new tinnitus assistive technology.

Abstract: Masking is widely used in the management of tinnitus, however, masking at the perceived spatial location of tinnitus has not been investigated. This article examines the development of a method for the spatial masking of tinnitus. This report consists of three studies: Study I is a proof of concept study comparing customized spatial masking to conventional bilateral masking; Study II is a prototype evaluation in which the spatial masking paradigm was compared to a bilaterally equal masker using iPods connected to hearing aids in a 4-week cross-over trial; and Study III is a 4-month crossover pilot study-using prototype hearing aid-based maskers, and in which three-dimensional (3D) masking (2 months) was compared to a Tinnitus Retraining Therapy (2 months). There was a preference for the 3D masking stimulus across all three studies. Individual changes in the Tinnitus Handicap Inventory (THI) after 2 weeks of trial (Study II) and Tinnitus Functional Index (TFI) after 2 months of trial (Study III) were observed without large group differences. The spatial masking concept was piloted successfully. The qualitative and quantitative results obtained indicate directions for future clinical trials and therapy development. This study indicates that spatial masking of tinnitus is feasible, of benefit to many participants, and warrants further trials.

Searchfield|Grant D|GD|
Kobayashi|Kei|K|
Hodgson|Shirley-Anne|SA|
Hodgson|Catherine|C|
Tevoitdale|Hannah|H|
Irving|Sam|S|


Inflammatory myofibroblastic tumor: molecular landscape, targeted therapeutics, and remaining challenges.

Abstract: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor of intermediate malignant potential that predominantly affects children, adolescents and young adults. IMT has a predilection for the lung, abdomen, pelvis, and retroperitoneum, however, can affect any part of the body. IMT is typically localized, and multifocal or metastatic disease is uncommon. Complete surgical resection is the treatment of choice when feasible. There is no established standard of care for unresectable and advanced IMT. Approximately half of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, and fusions involving ROS1, PDGFRβ, RET and NTRK have also been described. Given the molecular landscape of IMT, management of these tumors has evolved to include tyrosine kinase inhibitors and novel targeted therapeutics. This review highlights the molecular characteristics, evolution of targeted therapies and the remaining challenges in the management of IMT.

Mahajan|Priya|P| Casanova|Michela|M| Ferrari|Andrea|A| Fordham|Ashleigh|A| Trahair|Toby|T| Venkatramani|Rajkumar|R|

targeted therapy, crizotinib, ALK inhibition


Characterization and identification of three novel aldo-keto reductases from Lodderomyces elongisporus for reducing ethyl 4-chloroacetoacetate.

Abstract: Lodderomyces elongisporus LH703 isolated from soil samples contained three novel aldo-keto reductases (AKRs) (LEAKR 48, LEAKR 49, and LEAKR 50). The three enzymes were cloned, expressed, and purified to homogeneity for characterization. These three AKRs shared <40% amino acid identity with each other. LEAKR 50 was identified as a member of AKR3 family, whereas the other two LEAKRs were identified as members of two novel AKR families, respectively. All the three AKRs required nicotinamide adenine dinucleotide phosphate as a cofactor. However, they showed diverse characteristics, including optimum catalyzing conditions, resistance to adverse reaction conditions, and substrate specificity. LEAKR 50 was estimated to be a promising biocatalyst that could reduce ethyl 4-chloroacetoacetate with high enantiomeric excess (98% e. e.) and high activity residue under adverse conditions.

D000090:Acetoacetates
D000449:Aldehyde Reductase
D000074408:Aldo-Keto Reductases
D000595:Amino Acid Sequence
D003001:Cloning, Molecular
D005656:Fungal Proteins
D008969:Molecular Sequence Data
D009243:NAD
D012442:Saccharomycopsis

Characterization
Identification
Lodderomyces elongisporus
Ethyl 4-chloroacetoacetate
Aldo–keto reductase


Pathogen-Induced Epigenetic Modifications in Cancers: Implications for Prevention, Detection and Treatment of Cancers in Africa.

Abstract: Cancer is a major public health burden worldwide. Tumor formation is caused by multiple intrinsic and extrinsic factors. Many reports have demonstrated a positive correlation between the burden of infectious pathogens and the occurrence of cancers. However, the mechanistic link between pathogens and cancer development remains largely unclear and is subject to active investigations. Apart from somatic mutations that have been widely linked with various cancers, an appreciable body of knowledge points to alterations of host epigenetic patterns as key triggers for cancer development. Several studies have associated various infectious pathogens with epigenetic modifications. It is therefore plausible to assume that pathogens induce carcinogenesis via alteration of normal host epigenetic patterns. Thus, Africa with its disproportionate burden of infectious pathogens is threatened by a dramatic increase in pathogen-mediated cancers. To curb the potential upsurge of such cancers, a better understanding of the role of tropical pathogens in cancer epigenetics could substantially provide resources to improve cancer management among Africans. Therefore, this review discusses cancer epigenetic studies in Africa and the link between tropical pathogens and cancer burden. In addition, we discuss the potential mechanisms by which pathogens induce cancers and the opportunities and challenges of tropical pathogen-induced epigenetic changes for cancer prevention, detection and management.

epigenetics
cancer
tropical pathogens
pathogen-induced cancer


Myosin light chain kinase mediates intestinal barrier dysfunction following simulated microgravity based on proteomic strategy.

Abstract: Microgravity induces injury of intestinal barrier. However, the underlying mechanism remains unclear. The present study aimed to investigate the pathological change of intestinal mucosa induced by long term simulated microgravity and to explore its etiological mechanism using a proteomic approach. The well accepted tail-suspended rat model was used to simulate microgravity. The damage of rat small intestine was evaluated via histological and molecular test, and a label-free comparative proteomic strategy was used to determine the molecular mechanism. Simulated microgravity for 21 days damaged intestine barrier with decreased numbers of the goblet cells, large intercellular space, and down-regulated adhesion molecules, accompanied by increased intestinal permeability. Proteomic analysis identified 416 differentially expressed proteins and showed simulated microgravity dramatically down-regulated the adhesion molecules and deteriorated several pathways for metabolism, focal adhesion, and regulation of actin cytoskeleton. Western-blot analysis confirmed that myosin regulatory light chain (MLC) 12B was significantly down-regulated, while rho-associated protein kinase, myosin light chain kinase (MLCK), and phosphorylated MLC were dramatically up-regulated. Taken together, these data reveal that down-regulation of adhesion molecules and MLCK dependent up-regulation MLC phosphorylation mediate intestinal barrier dysfunction during simulated microgravity injury. Our results also indicate that regulation of epithelial MLCK is a potential target for the therapeutic treatment of microgravity injury.

Wang|Shibo|S|
Wang|Rui|R|
Li|George Q|GQ|
Cho|Jun-Lae|JL|
Deng|Yulin|Y|
Li|Yujuan|Y|

Myosin light chain kinase
Microgravity
Proteomics
Intestinal barrier injury


Human African Trypanosomiasis - A rare case report from India.

Abstract: A young female patient from Ahmedabad city presented with acute febrile illness and bicytopenia (leukopenia and thrombocytopenia). She returned to India after recent visit to East Africa. Human African Trypanosomiasis (Sleeping sickness) was diagnosed by identification of Trypanosoma brucei rhodesiense in peripheral blood smear. She treated successfully with suramin. In India, we account this as second case of HAT after first report before 18 years in the published literature.

Shah|Vipul V|VV|
Patel|Vipul M|VM|
Vyas|Pultsya|P|

Human African Trypanosomiasis
Sleeping sickness
Trypanosoma brucei rhodesiense


Comparison of Single Nucleotide Polymorphism genotyping of CYP2C19 by Loop-mediated isothermal amplification and real-time PCR melting curve analysis.

Abstract:
BACKGROUND
CYP2C19, a member of cytochrome P450 enzymes, is involved in various drug metabolisms, such as Clopidogrel. Common Single Nucleotide Polymorphisms (SNPs) of CYP2C19 gene, CYP2C19*2 and CYP2C19*3, are liable for the poor metabolism of Clopidogrel. It is crucial to identify poor metabolizers for alternative treatment as poor metabolism of Clopidogrel has been shown to correlate with worse clinical outcome in acute coronary syndrome (ACS) patients.

METHOD
A genotyping method, Loop-mediated isothermal amplification (LAMP) was employed in this study. CYP2C19*2 and CYP2C19*3 were adapted from Iwasaki M. et al. with modifications in the reaction mixtures and end-point detection method where simpler visual detection using SYBR® Safe was employed instead of a more technical and equipment demanding real-time PCR. Real-time PCR melting curve analysis is a common method for SNPs analysis and hence chosen as a reference for results obtained from the LAMP assay.

RESULTS
The CYP2C19-LAMP assay successfully detected CYP2C19*2 and CYPC19*3 mutants. The typing results of CYP2C19-LAMP assay, performed in triplicates, were concordant with the real-time PCR melting curve analysis results.

CONCLUSION
CYP2C19-LAMP assay using SYBR® Safe dye for visual detection of end-point result is a simple, rapid and cost-effective method for CYP2C19 genotyping.

Kwong|K M|KM|
Tam|C C|CC|
Chan|Raymond|R|
Lee|Stephen W L|SWL|
Ip|P|P|
Kwok|Janette|J|

D021141:Nucleic Acid Amplification Techniques

Single Nucleotide Polymorphism
Genotyping
CYP2C19
Loop-mediated isothermal amplification
Real-time PCR melting curve analysis
Drug metabolism
Clopidogrel
Acute coronary syndrome


MicroRNA-298 inhibits malignant phenotypes of epithelial ovarian cancer by regulating the expression of EZH2.

Abstract: MicroRNA (miRNA or miR)-298 has been reported to be downregulated and to modify the expression of the polycomb protein enhancer of zeste 2 (EZH2) in recurrent epithelial ovarian cancer (EOC). To date, no functional evidence of a miR-298-EZH2 axis in EOC has been documented. The present study aimed to investigate the associations of miR-298 and/or EZH2 expression with clinicopathological features of EOC patients, and revealed their roles in cell motility based on EOC cell lines. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of miR-298 and EZH2 messenger RNA in human EOC tissues and cell lines. Wound healing and transwell assays were performed to determine the function of the miR-298-EZH2 axis on cell migration and invasion, respectively. Compared with normal tissues, miR-298 expression was significantly downregulated, while EZH2 expression was significantly upregulated, in human EOC tissues (both P=0.001). In addition, miR-298 downregulation and EZH2 upregulation were significantly associated with high clinical stage (both P=0.01) and pathological grade (both P=0.02) of EOC patients. Furthermore, the ectopic expression of miR-298 could efficiently inhibit cell migration and invasion. Notably, the overexpression of EZH2 could restore the cell migration and invasion abilities suppressed by miR-298. Our data offer convincing evidence that the dysregulation of the miR-298-EZH2 axis may be important in tumor progression of EOC patients. The present study also confirmed a tumor-suppressive role of miR-298 in modulating EOC cell motility by regulating the expression of EZH2, implying its potential as a novel miRNA-based therapeutic target for the treatment of human EOC.

microRNA-298
epithelial ovarian cancer
enhancer of zeste 2
clinicopathological feature
migration
invasion


Elevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study.

Abstract:
BACKGROUND
Individuals with autoimmune diseases and severe infections have persistent or acutely elevated inflammatory biomarkers and increased risk of schizophrenia. We tested the hypothesis that baseline elevated plasma levels of the inflammatory biomarker, C-reactive protein (CRP), associate with increased risk of late- and very-late-onset schizophrenia in the general population, and if such an association possibly is causal.

METHOD
We analyzed data from 78 810 men and women, aged 20-100 years, from 2 large population studies. Endpoints were hospitalization with schizophrenia and schizophrenia and schizophrenia-like psychosis combined. We performed prospective and cross-sectional analyses adjusted for potential confounders with up to 20 years of follow-up. Furthermore, we used genetic variants influencing plasma CRP levels to perform a Mendelian randomization study.

RESULTS
Age- and gender-adjusted hazard ratios vs individuals in the first quartile of CRP were 1.7 (95% CI: 0.3-8.9) for second quartile, 2.1 (0.4-10) for third quartile, and 11 (2.8-40) for fourth quartile individuals. The corresponding hazard ratio for fourth quartile individuals after multifactorial adjustment was 5.9 (1.4-24). Furthermore, individuals with vs without schizophrenia had 63% increased plasma levels of CRP (P = 1 × 10(-4)). Finally, when CRP was on a continuous scale, a doubling in CRP yielded an age- and gender-adjusted observational OR of 1.5 (1.3-1.8) and a corresponding causal OR of 1.4 (0.5-4.3) (observed vs causal: P = .89).

CONCLUSION
Baseline elevated plasma CRP is associated with a 6- to 11-fold increased risk of late- and very-late-onset schizophrenia in the general population. We cannot exclude that this is a causal association. These are novel findings.

Wium-Andersen|Marie Kim|MK|
Ørsted|David Dynnes|DD|
Nordestgaard|Børge Grønne|BG|

schizophrenia genetics epidemiology inflammation


Plant-eating carnivores: Multispecies analysis on factors influencing the frequency of plant occurrence in obligate carnivores.

Abstract: Plant-eating behavior is one of the greatest mysteries in obligate carnivores. Despite unsuitable morphological and physiological traits for plant consumption, the presence of plants in scat or stomach contents has been reported in various carnivorous species. However, researchers' interpretations of this subject are varied, and knowledge about it is scarce, without any multispecies studies. This study assessed the extent of variation in the frequency of plant occurrence in scat and stomach contents, as well as its relationship with various factors in 24 felid species using data from 213 published articles. Since the frequency of plant occurrence has not always been reported, we created two-part models and estimated parameters in a Bayesian framework. We found a significant negative relationship between the frequency of plant occurrence and body mass. This may be because plant-eating behavior reduces the energy loss caused by parasites and increases the efficiency of energy intake, which has a greater importance in smaller animals that have relatively high metabolic rates. This exploratory study highlights the importance of considering plant consumption in dietary studies on carnivorous species to understand the adaptive significance of this behavior and the relationship between obligate carnivores and plants.


Stress-Responsive Periplasmic Chaperones in Bacteria.

Abstract: Periplasmic proteins are involved in a wide range of bacterial functions, including motility, biofilm formation, sensing environmental cues, and small-molecule transport. In addition, a wide range of outer membrane proteins and proteins that are secreted into the media must travel through the periplasm to reach their final destinations. Since the porous outer membrane allows for the free diffusion of small molecules, periplasmic proteins and those that travel through this compartment are more vulnerable to external environmental changes, including those that result in protein unfolding, than cytoplasmic proteins are. To enable bacterial survival under various stress conditions, a robust protein quality control system is required in the periplasm. In this review, we focus on several periplasmic chaperones that are stress responsive, including Spy, which responds to envelope-stress, DegP, which responds to temperature to modulate chaperone/protease activity, HdeA and HdeB, which respond to acid stress, and UgpB, which functions as a bile-responsive chaperone.

periplasmic chaperone
Spy
DegP
HdeA
HdeB
UgpB


Efficacy outcomes in the MDD-1 India study: First episode major depressive disorder outcomes in antidepressant-treated real-world patients in India.

Abstract:
OBJECTIVES
Little is known about the outcome of major depressive disorder in India, especially in primary care contexts not usually associated with research. This large, prospective, naturalistic observational study examined the feasibility of studying first-episode major depressive disorder outcomes in such contexts, and examined outcomes after antidepressant drug treatment.

METHODS
A convenience sample of 205 psychiatrists across India each recruited five adults with first-episode major depressive disorder. No patient had clinically significant suicidal ideation, psychotic symptoms, or significant medical or psychiatric comorbidity. Patients were naturalistically treated with antidepressant medication and rated using the Montgomery-Asberg Depression Rating Scale and other instruments, including patient-reported outcome measures. Assessments were obtained at baseline and at a 6-week follow-up.

RESULTS
Of 900 patients recruited, 92 did not meet selection criteria, and there were 10 dropouts, leaving 798 evaluable patients. The most common antidepressants received were desvenlafaxine, vilazodone, and escitalopram. The primary outcome, response (50% attenuation of Montgomery-Asberg Depression Rating Scale score), was identified in 66.1% of the sample. The patient-reported outcome measures-defined response rate was 53.1%. Remission (endpoint Montgomery-Asberg Depression Rating Scale score of 10 or less) was observed in 36.7% of the sample. Response (but not remission) was very slightly but significantly better in women than in men on some but not all measures.

CONCLUSIONS
It is feasible to conduct simple but meaningful observational studies in primary care contexts that are not usually associated with research. About two-thirds of real-world adults in primary care in India diagnosed with uncomplicated first-episode major depressive disorder respond to 6 weeks of antidepressant medications; about one-third of the adults remit.

D011569:Psychiatric Status Rating Scales

gender difference in antidepressant response


A comparison of quality of life and resilience in menopausal women with and without a history of gynaecological cancer.

Abstract:
BACKGROUND AND OBJECTIVES
Resilience is a dynamic process that implies positive adaptation to adversity, and it is tested in stressful situations. In this study we compared resilience and menopause-related quality of life in women with and without a history of gynaecological cancer.

METHODS
A cross-sectional study was conducted with a total of 293 participants, all of them menopausal women: 80 cancer survivors and 213 without a history of cancer. Participants completed the 14-item Wagnild and Young Resilience Scale (WYRS-14) and the 16-item short form Cervantes (Cervantes-SF-16) questionnaire (on which a lower score indicates a higher menopause-related quality of life), and sociodemographic data were collected.

RESULTS
Resilience was significantly higher in the cancer survivors than in the menopausal women without a history of cancer: their total WYRS-14 scores were 86 points [72.25-90.00] and 80 points [69.80-88], respectively. Quality of life for cancer survivors was significantly worse than for women without a history of cancer: their total Cervantes-SF-16 scores were 45.01 [27.19-58.34] and 32.37 [20.00-44.80], respectively. Among the cancer survivors, women with a high resilience score had a better quality of life than those with a low resilience score: the groups' respective scores on the Cervantes-SF-16 total score were 35.98 [25.84-53.00] and 64.59 [51.81-76.68].

CONCLUSIONS
A history of cancer significantly affected women's menopause-related quality of life. Cancer had an impact on resilience. Highly resilient menopausal women with a history of gynaecological cancer had a better menopause-related quality of life than less resilient women with a history of gynaecological cancer.

Oliva|Agustin|A|
García-Cebrián|Jose M|JM|
Calatayud|Eva F|EF|
Serrano-García|Irene|I|
Herraiz|Miguel A|MA|
Coronado|Pluvio J|PJ|


Adenosine as a Marker and Mediator of Cardiovascular Homeostasis: A Translational Perspective.

Abstract: Adenosine, a purine nucleoside, is produced broadly and implicated in the homeostasis of many cells and tissues. It signals predominantly via 4 purinergic adenosine receptors (ADORs) - ADORA1, ADORA2A, ADORA2B and ADOosine signaling, both through design as specific ADOR agonists and antagonists and as offtarget effects of existing anti-platelet medications. Despite this, adenosine has yet to be firmly established as either a therapeutic or a prognostic tool in clinical medicine to date. Herein, we provide a bench-to-bedside review of adenosine biology, highlighting the key considerations for further translational development of this proRA3 in addition to non-ADOR mediated effects. Through these signaling mechanisms, adenosine exerts effects on numerous cell types crucial to maintaining vascular homeostasis, especially following vascular injury. Both in vitro and in vivo models have provided considerable insights into adenosine signaling and identified targets for therapeutic intervention. Numerous pharmacologic agents have been developed that modulate adenmising molecule.

Simard|Trevor|T|
Jung|Richard|R|
Labinaz|Alisha|A|
Faraz|Mohammad Ali|MA|
Ramirez|F Daniel|FD|
Di Santo|Pietro|P|
Pitcher|Ian|I|
Motazedian|Pouya|P|
Gaudet|Chantal|C|
Rochman|Rebecca|R|
Marbach|Jeffrey|J|
Boland|Paul|P|
Sarathy|Kiran|K|
Alghofaili|Saleh|S|
Russo|Juan J|JJ|
Couture|Etienne|E|
Beanlands|Rob S|RS|
Hibbert|Benjamin|B|

Adenosine cardiovascular biomarker pre-clinical restenosis translational.


Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil.

Abstract: Donepezil (DPZ) is widely used in the treatment of Alzheimer's disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood⁻brain barrier (BBB) possible. The aim of this study was to develop a nanoemulsion (NE) as well as a nanoemulsion with a combination of bioadhesion and penetration enhancing properties (PNE) in order to facilitate the transport of DPZ from nose-to-brain. Composition of NE was established using three pseudo-ternary diagrams and PNE was developed by incorporating Pluronic F-127 to the aqueous phase. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined for both formulations. The tolerability was evaluated by in vitro and in vivo models. DPZ-NE and DPZ-PNE were transparent, monophasic, homogeneous, and physically stable with droplets of nanometric size and spherical shape. DPZ-NE showed Newtonian behavior whereas a shear thinning (pseudoplastic) behavior was observed for DPZ-PNE. The release profile of both formulations followed a hyperbolic kinetic. The permeation and prediction parameters were significantly higher for DPZ-PNE, suggesting the use of polymers to be an effective strategy to improve the bioadhesion and penetration of the drug through nasal mucosa, which consequently increase its bioavailability.

Espinoza|Lupe Carolina|LC|
Silva-Abreu|Marcelle|M|
Clares|Beatriz|B|
Rodríguez-Lagunas|María José|MJ|
Halbaut|Lyda|L|
Cañas|María-Alexandra|MA|
Calpena|Ana Cristina|AC|

nose-to-brain
Donepezil
nanoemulsion
Pluronic F-127
Alzheimer’s disease
mucoadhesion


Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension.

Abstract:
BACKGROUND
Hypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established. This study compared the plasma and adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in age- and body mass index-matched subjects with and without hypertension.

METHODS
A total of 119 subjects, including 69 hypertensive and 50 non-hypertensive subjects, were enrolled. ANGPTL3, ANGPTL4 and ANGPTL8 plasma levels were measured by ELISA, whereas their levels in adipose tissue were assessed via real-time PCR.

RESULTS
We found that ANGPTL4 (202.49 ± 17.44 ng/mL vs. 160.64 ± 10.36 ng/mL, p = 0.04) and ANGPTL8 levels (2310.96 ± 194.88 pg/mL vs. 1583.35 ± 138.27 pg/mL, p = 0.001) were higher in hypertensive subjects than non-hypertensive subjects. However, ANGPTL3 levels were not significantly different between the two populations. Similarly, ANGPTL4 and ANGPTL8 levels were also elevated in subjects with T2D and hypertension than in those with T2D but not hypertension. Additionally, people with highest tertiles of ANGPTL8 had higher odds of having hypertension (odd ratio [OR] = 3.8, 95% confidence interval [CI] = (1.5-9.8), p-Value = 0.005. Similar to its plasma levels, ANGPTL4 and ANGPTL8 were higher in adipose tissue.

CONCLUSIONS
In conclusion, our data illustrate that ANGPTL4 and ANGPTL8 levels in both plasma and adipose tissues are increased in subjects with hypertension. The elevated levels of ANGPTL4 and ANGPTL8 in hypertensive subjects highlight their potential involvement, their potential role as biomarkers for hypertension and their therapeutic value in hypertension given their roles in regulating lipid metabolism.

D000273:Adipose Tissue
D000328:Adult
D000091303:Angiopoietin-Like Protein 3
D000075803:Angiopoietin-Like Protein 4
D000091306:Angiopoietin-Like Protein 8
D000075802:Angiopoietin-like Proteins
D016022:Case-Control Studies
D003924:Diabetes Mellitus, Type 2
D005260:Female
D015870:Gene Expression
D006801:Humans
D006973:Hypertension
D016015:Logistic Models
D008297:Male
D008875:Middle Aged
D036361:Peptide Hormones

Hypertension
Angiopoietin-like proteins
Type-2 diabetes


Agreement between manual relaxometry and semi-automated scanner-based multi-echo Dixon technique for measuring liver T2* in a pediatric and young adult population.

Abstract:
BACKGROUND
Commercially available 3D multi-echo Dixon (mDixon) sequences provide parametric maps of liver T2*, obviating manual curve fitting that is often required with conventional gradient recalled echo (GRE)-based multi-echo relaxometry, potentially simplifying clinical work flow.

OBJECTIVE
The purpose of our study was to compare T2* values generated by a 3D mDixon sequence to values generated by GRE-based T2* relaxometry with manual curve fitting in a pediatric and young adult population.

MATERIALS AND METHODS
We reviewed clinical MRI exams performed at 1.5T for liver iron content estimation between February 2015 and June 2016 that included both mDixon and multi-echo GRE pulse sequences. We obtained mean T2* measurements based on each sequence by drawing regions of interest on each of four axial slices through the mid-liver. We compared mDixon-based and GRE-based T2* measurements using paired t-tests and assessed agreement using single-measure intra-class correlation coefficients and Bland-Altman difference plots.

RESULTS
One hundred nine patients met inclusion criteria (site 1=82; site 2=27). Mean age was 12.4±5.8 years, and 42 subjects (39%) were female. There was no statistically significant difference in mean T2* values for the two sequences (pooled means: 11.7±11.0 [GRE] vs. 11.7±10.9 ms [mDixon]; P=0.93). There was excellent absolute agreement between sequences (intraclass correlation coefficient [ICC]=0.98 for patients at both sites, confidence interval [CI]: 0.97-0.98 with mean bias of 0.0 ms [-4.2 ms to +4.2 ms]).

CONCLUSION
3D mDixon is accurate for measuring liver T2* and can likely replace 2D GRE-based relaxometry.

Serai|Suraj D|SD|
Smith|Ethan A|EA|
Trout|Andrew T|AT|
Dillman|Jonathan R|JR|

Relaxometry
Liver
Iron
Children
Magnetic resonance imaging
Multi-echo Dixon sequence
T2* imaging


A need for "good eyes": Experiences told by patients diagnosed with psychosis.

Abstract: This study highlights experiences of psychiatric care described by patients diagnosed with psychosis. The aim was to investigate how patients, based on earlier experiences, described their wishes and needs regarding the psychiatric care system. Data comprised material from four focus groups; analysis used an inductive thematic approach. Relationships with staff emerged as a recurring theme. During periods of psychosis, patients needed staff to act as "parental figures," providing care, safety, and help in dealing with overwhelming stimulation from the outside word. In the ensuing struggle to devise a livable life, the need for relationships recurred. In this phase, staff needed to give their time, provide support through information, and mirror the patient's capacity and hope. The patient's trials were described as threatened by a lack of continuity and non-listening professionals. It was important for staff to listen and understand, and to see and respect the patients' viewpoints.

psychiatric care
Relationship
respect
patient experiences
thematic analyses


Two transcripts of HMG-CoA reductase related with developmental regulation from Scylla paramamosain: Evidences from cDNA cloning and expression analysis.

Abstract: 3-Hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases (HMGRs), which catalyze the conversion of HMG-CoA to mevalonate, may have an important role in the synthesis of methyl farnesoate (MF). In this study, we obtained two HMGR cDNA sequences termed Sp-HMGR1 (membrane-bound form) and Sp-HMGR2 (soluble form), which encode 967 and 654 amino acids, respectively. The two cDNAs possess entirely identical sequences except that Sp-HMGR1 is 1,382 bp, which encodes a sterol-sensed domain (SSD; a membrane-bound domain) and was first found in crustacean HMGR, larger than Sp-HMGR2. Thus, it was deduced that these cDNAs might be derived from a single genomic DNA sequence. Sp-HMGRs have the typical features of the HMGR class of proteins. However, residue 844 in Sp-HMGR1, which is usually occupied by a Ser residue in other species, has an unusual Ala substitution. This Ser is thought to be involved in enzyme activity regulation by reversible phosphorylation. A putative "PEST" sequence that, until now, has only been found in crustacean species was also identified in the C-terminus of both transcripts, and a sterol-sensing domain, which was first found in crustacean species, was identified in Sp-HMGR1; these findings suggest that Sp-HMGR might function in some special regulatory mechanism. Furthermore, the quantitative real-time polymerase chain reaction results showed that the two transcripts have different expression patterns; Sp-HMGR2 was mainly expressed in the mandibular organ (MO) of adult crabs, whereas Sp-HMGR1 was mainly expressed in other tissues and fertilized eggs up until the fourth juvenile crab stage. The fluctuating gene expression seemed to suggest a relationship between Sp-HMGRs and the development of the crab, especially during the larval stage. Besides, the fluctuation of Sp-HMGR1 in ovary, brain, and thoracic ganglia during the ovary development seemed to have some correlation with the nutrition accumulation of ovaries, whether the SSD domain evolved in this process deserve further investigation. Moreover, it remains unclear whether the significant variation in ovary, brain, and thoracic ganglia during ovary development suggests that other tissues in addition to the MO could synthesize MF.

Zhao|Ming|M| Jiang|Keji|K| Song|Wei|W| Ma|Chunyan|C| Wang|Jing|J| Meng|Yongyong|Y| Wei|Hongqing|H| Chen|Kai|K| Qiao|Zhenguo|Z| Zhang|Fengying|F| Ma|Lingbo|L|

D018507:Gene Expression Regulation, Developmental


Energizing Genetics and Epi-genetics: Role in the Regulation of Mitochondrial Function.

Abstract: Energy metabolism and mitochondrial function hold a core position in cellular homeostasis. Oxidative metabolism is regulated at multiple levels, ranging from gene transcription to allosteric modulation. To accomplish the fine tuning of these multiple regulatory circuits, the nuclear and mitochondrial compartments are tightly and reciprocally controlled. The fact that nuclear encoded factors, PPARγ coactivator 1α and mitochondrial transcription factor A, play pivotal roles in the regulation of oxidative metabolism and mitochondrial biogenesis is paradigmatic of this crosstalk. Here we provide an updated survey of the genetic and epigenetic mechanisms involved in the control of energy metabolism and mitochondrial function. Chromatin dynamics highly depends on post-translational modifications occurring at specific amino acids in histone proteins and other factors associated to nuclear DNA. In addition to the well characterized enzymes responsible for histone methylation/demethylation and acetylation/deacetylation, other factors have gone on the "metabolic stage". This is the case of the new class of α-ketoglutarate-regulated demethylases (Jumonji C domain containing demethylases) and of the NAD+-dependent deacetylases, also known as sirtuins. Moreover, unexpected features of the machineries involved in mitochondrial DNA (mtDNA) replication and transcription, mitochondrial RNA processing and maturation have recently emerged. Mutations or defects of any component of these machineries profoundly affect mitochondrial activity and oxidative metabolism. Finally, recent evidences support the importance of mtDNA packaging in replication and transcription. These observations, along with the discovery that non-classical CpG islands present in mtDNA undergo methylation, indicate that epigenetics also plays a role in the regulation of the mitochondrial genome function.

Audano|Matteo|M|
Ferrari|Alessandra|A|
Fiorino|Erika|E|
Kuenzl|Martin|M|
Caruso|Donatella|D|
Mitro|Nico|N|
Crestani|Maurizio|M|
De Fabiani|Emma|E|

Energy metabolism
Mitochondrial biogenesis
Chromatin
Transcription.
DNA modification
Histone modification


LncRNA AC105942.1 Downregulates hnRNPA2/B1 to Attenuate Vascular Smooth Muscle Cells Proliferation.

Abstract: The abnormal proliferation of vascular smooth muscle cells (VSMCs) is crucial in the atherosclerosis. Although long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their roles in activation of VSMCs proliferation and vascular disorder diseases are not well understood. In addition, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) was reported to participate in lncRNAs-mediated function. Herein, we propose to investigate the role of lncRNA AC105942.1 and hnRNPA2/B1 in pathological VSMCs proliferation and the possible mechanisms in vitro. We have identified that lncRNA AC105942.1 was downregulated and hnRNPA2/B1 was upregulated in atherosclerotic plaques compared with normal artery tissues. Enhanced lncRNA AC105942.1 could noticeably inhibit Ang II-induced VSMCs proliferation. Further investigation suggested that lncRNA AC105942.1 could downregulate the expression of hnRNPA2/B1 and then regulate the level of CDK4 and p27. Taken together, our study indicated that lncRNA AC105942.1 downregulated hnRNPA2B1 to protect against the atherosclerosis by suppressing VSMCs proliferation. LncRNA AC105942.1 and hnRNPA2/B1 could represent potential therapeutic and diagnostic targets to atherosclerosis-related diseases.

Zhang|Ru-Yi|RY| Wu|Chang-Meng|CM| Hu|Xiu-Mei|XM| Lin|Xiao-Min|XM| Hua|Yu-Neng|YN| Chen|Jun-Jiang|JJ| Ding|Li|L| He|Xin|X| Yang|Biao|B| Ping|Bao-Hong|BH| Zheng|Lei|L| Wang|Qian|Q|

D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B

lncRNA AC105942.1
hnRNPA2/B1
vascular smooth muscle cell
cell proliferation
long noncoding RNA


Elicitation and prioritization of requirements for electronic health records for oncology in low resource settings: A concept mapping study.

Abstract:
BACKGROUND
Understanding functional and non-functional requirements is essential to successfully implement electronic medical record (EMR) systems. Actual requirements will be different for different contexts.

OBJECTIVE
To elicit and prioritize requirements for implementing EMRs in oncology in low and middle income countries (LMICs), and to relate these to requirements from high-income countries.

PARTICIPANTS AND SETTING
Cancer care stakeholders including oncologists, general doctors, nurses, biostatisticians, information technologists, from different LMICs, were involved.

METHODS
Concept mapping was used. Statements of requirements were obtained during focus group discussions (FGDs) and interviews. Using surveys, the requirements were clustered and ranked on importance and feasibility. Data were analyzed in SPSS using agglomerative hierarchical clustering and multidimensional scaling, to create cluster maps and go-zone maps reflecting the relationships between the requirements and their prioritization.

RESULTS
Four FGD sessions, with twenty participants, were conducted. In addition, six participants were interviewed. Twenty-two participants clustered the requirements and sixty-three participants ranked them on importance and feasibility. One hundred and sixty requirement statements were generated which were reduced to sixty-four after de-duplication and merging. Nine clusters were obtained encompassing the following domains, in order of importance: Security, Conducive organization, Management/Governance, General EMR functionalities, Computer infrastructure, Data management, Usability, Oncology decision support, and Ancillary requirements. On ranking, the requirements scored between 3.74 and 4.80 on importance, and between 3.55 and 4.46 on feasibility, on a 5-point Likert scale. We generated concept maps for use when communicating with stakeholders.

CONCLUSION
For oncology EMRs in LMICs, requirements overlap those from high-income countries, but generic EMR functionalities, Infrastructural and organizational requirements are still considered priority in LMICs compared to oncology-specific requirements or advanced EMR features e.g. computerized decision support or interoperability. Concept mapping is a fast and cost-effective method for eliciting and prioritizing EMR requirements in a user-centered manner.

Kabukye|Johnblack K|JK|
de Keizer|Nicolet|N|
Cornet|Ronald|R|

D016000:Cluster Analysis
D057286:Electronic Health Records
D005260:Female
D017144:Focus Groups
D006295:Health Resources
D006801:Humans
D008297:Male
D008495:Medical Oncology
D011795:Surveys and Questionnaires

Electronic health record
Developing countries
Medical oncology
Requirements engineering


Measuring consumer emotional response and acceptance to sustainable food products.

Abstract: With current global challenges such as population growth, climate change and water scarcity, it is critical to develop sustainable strategies to achieve food security. One way to tackle this is by developing new products that use alternative and more sustainable ingredients. Bambara groundnut is a low-impact African legume as it can be grown on marginal soils and is resistant to high temperatures. The aim of this study was to investigate UK consumer acceptability and emotional response to snack products containing Bambara groundnut flour as an alternative sustainable ingredient. A key objective was to understand the contribution that measuring emotional response would reveal. Additionally the impact of extrinsic information on consumer acceptability and emotional response to snack products was investigated by sharing information concerning Bambara groundnut's sustainability and nutritional credentials. 100 UK participants were recruited to evaluate two biscotti and two cracker products. For each category a standard product made from standard ingredients sourced commercially, and one made replacing some of standard flour with Bambara flour were obtained. For each sample, participants were asked to rate their overall liking and emotional response based on sensory properties of the product (the blind condition). Participants were invited back for a second session, where they were informed about global resource challenges, and the sustainable features and nutritional value of Bambara, and which products contained this as an ingredient (informed condition). Under the blind condition, no significant differences in overall liking were observed between standard and Bambara products, indicating UK consumers accept the sensory properties of products that contain Bambara flour. Interestingly, the extrinsic information shifted consumer emotional response towards more positive emotions and less negative emotions when consuming products containing Bambara flour. It also made them felt less guilty when consuming the Bambara products, suggesting consumers engage with the idea of sustainable ingredients, and that this sustainable ingredient has potential for future new product development. It also highlighted the value of measuring emotional response for novel products to understand what may drive purchase behaviour when products are matched for liking. Food neophobia status did not impact product acceptability and emotional response between Bambara and standard products, however overall a lower emotional response was found for medium neophobic consumers in general who are more likely to evade novel products.

Yang|Qian|Q| Shen|Yuchi|Y| Foster|Tim|T| Hort|Joanne|J|

Emotion response
Sustainable ingredient
Bambara groundnut
Liking
Food neophobia


Cost-effectiveness of an educational healthcare circuit for bariatric surgery in France.

Abstract:
OBJECTIVES
An educational healthcare circuit (EHC) is proposed with the objective of preventing weight recovery of patients after bariatric surgery through education and lifestyle change. The objective of this study was to measure the viability of the EHC (shared medical appointments [SMAs] combined with bariatric surgery) through cost-effectiveness analysis. The EHC presented in this study is innovative because it offers a multidisciplinary approach based on medical, psychological and dietetic expertise to combat obesity. The strategy is to give the patient a diagnosis and then a personalised follow-up.

STUDY DESIGN
A mathematical model based on a decision tree (1 year) and a Markov model (10 years) to measure the efficiency and cost of an EHC in comparison with the customary care offered in France were built.

METHODS
The effects of the EHC were observed for the prevalence of type 2 diabetes and the risk of cardiovascular disease. The chosen financial perspective is from the point of view of the French social security system.

RESULTS
The EHC records an incremental cost-effective ratio (ICER) of € 48,315.43 per quality-adjusted life year (QALY) over a 1-year horizon and € 28,283.77 per QALY over 10 years (with discount rate of 8%: € 25,362.85 per QALY).

CONCLUSION
The results suggest that an EHC is more expensive yet more effective than usual care. That is, in the short term, the costs are high, but at 10 years, the treatment is cost-effective, representing a feasible alternative for those patients who qualify for bariatric surgery in France.

Duenas|A|A|
Di Martinelly|C|C|
Aelbrecht|A|A|
Allard|P-E|PE|
Rousseaux|J|J|

Cost-effectiveness
Bariatric surgery
Obesity
Type 2 diabetes
Cardiovascular diseases


Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition.

Abstract: The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy. • Octyl syringate, a phenolic derivate, is preferentially cytotoxic to various cancer cells. • Octyl syringate destabilizes the lysosomal function. • Octyl syringate blocks the autophagic flux. • Octyl syringate is a potential candidate compound for cancer therapy.

Won|Minho|M|
Choi|Sunkyung|S|
Cheon|Seonghye|S|
Kim|Eun-Mi|EM|
Kwon|Taeg Kyu|TK|
Kim|Jaewhan|J|
Kim|Yong-Eun|YE|
Sohn|Kyung-Cheol|KC|
Hur|Gang Min|GM|
Kim|Kee K|KK|

Octyl syringate
Autophagic flux
Non-apoptotic cell death
Lysosomal dysfunction
Lysosome target therapy


Eating behavior and body composition across childhood: a prospective cohort study.

Abstract:
BACKGROUND
Although many cross-sectional studies reported that children with overweight or obesity show more food approaching and less food avoidant eating behaviors, there is a lack of replication in longitudinal studies. Therefore, the question remains whether healthcare professionals should target eating behaviors in childhood obesity interventions and prevention. We aimed to examine the longitudinal and possible bi-directional associations between eating behavior and body composition across childhood.

METHODS
Data was included from 3331 children participating in the Generation R Study. At 4 and 10 years, mothers reported on the Child Eating Behavior Questionnaire including the subscales Food Responsiveness, Enjoyment of Food, Emotional Overeating and Satiety Responsiveness, and children's BMI was measured. Body composition, consisting of Fat Mass Index and Fat Free Mass Index was measured at 6 and 10 years with Dual-energy-X-ray-Absorptiometry scans.

RESULTS
Cross-lagged models including both directions of the BMI - eating behavior association showed that a higher BMI at the age of 4 years predicted more food responsiveness and enjoyment of food and less satiety responsiveness at 10 years (e.g. satiety responsiveness:β = - 0.10, 95% CI = - 0.14, - 0.07), but no associations were found in the opposite direction. For emotional overeating, however, a bi-directional association was found with BMI predicting more emotional eating and vice versa. Multivariable linear regression analyses showed that associations were stronger for Fat Mass Index than for Fat Free Mass Index.

CONCLUSIONS
Results showed that a higher BMI, and particularly higher fat mass, at pre-school age predicted more food approaching and less food avoidant eating behaviors at the age of 10 years, rather than the hypothesized reverse direction. This suggests that increased adiposity in early childhood might upregulate appetite and related eating behaviors.

Derks|Ivonne P M|IPM|
Sijbrands|Eric J G|EJG|
Wake|Melissa|M|
Qureshi|Farah|F|
van der Ende|Jan|J|
Hillegers|Manon H J|MHJ|
Jaddoe|Vincent W V|VWV|
Tiemeier|Henning|H|
Jansen|Pauline W|PW|

Eating behaviors
Cohort
Longitudinal
BMI
Fat mass
Adiposity
Appetite


The utility of the brain trauma evidence to inform paramedic rapid sequence intubation in out-of-hospital stroke.

Abstract:
BACKGROUND
Rapid sequence intubation (RSI) is used to secure the airway of stroke patients. Randomized controlled trial evidence exists to support the use of paramedic RSI for traumatic brain injury (TBI), but cannot necessarily be applied to stroke RSI because of differences between the stroke and TBI patient. To understand if the TBI evidence can be used for stroke RSI, we analysed a retrospective cohort of TBI and strokes to compare how survival is impacted differently by RSI when comparing strokes and TBI.

METHODS
This study was a retrospective analysis of 10 years of in-hospital and out-of-hospital data for all stroke and TBI patients attended by Ambulance Victoria, Australia. Logistic regression predicted the survival for ischemic and haemorrhagic strokes as well as TBI. The constituents of RSI, such a medications, intubation success and time intervals were analysed against survival using interactions to asses if RSI impacts survival differently for strokes compared to TBI.

RESULTS
This analysis found significant interactions in the RSI-only group for age, number of intubation attempts, atropine, fentanyl, pulse rate and perhaps scene time and time- to-RSI. Such interactions imply that RSI impact survival differently for TBI versus strokes. Additionally, no significant difference in survival for TBI was found, with a - 0.7% lesser survival for RSI compared to no-RSI; OR 0.86 (95% CI 0.67 to 1.11; p = 0.25). Survival for haemorrhagic stroke was - 14.1% less for RSI versus no-RSI; OR 0.44 (95% CI 0.33 to 0.58; p = 0.01) and was - 4.3%; OR 0.67 (95% CI 0.49 to 0.91; p = 0.01) lesser for ischemic strokes.

CONCLUSIONS
Rapid sequence intubation and related factors interact with stroke and TBI, which suggests that RSI effects stroke survival in a different way from TBI. If RSI impact survival differently for strokes compared to TBI, then perhaps the TBI evidence cannot be used for stroke RSI.

D000079603:Rapid Sequence Induction and Intubation

Paramedic
Traumatic brain injury
Stroke, rapid sequence intubation


AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?

Abstract: The serine/threonine kinase AKT is a key component of the PI3K/AKT/mTOR signaling pathway as it exerts a pivotal role in cell growth, proliferation, survival, and metabolism. Deregulation of this pathway is a common event in breast cancer including hormone receptor-positive (HR+) disease, HER2-amplified, and triple negative tumors. Hence, targeting AKT represents an attractive treatment option for many breast cancer subtypes, especially those resistant to conventional treatments. Several AKT inhibitors have been recently developed and two ATP-competitive compounds, capivasertib and ipatasertib, have been extensively tested in phase I and II clinical trials either alone, with chemotherapy, or with hormonal agents. Additionally, phase III trials of capivasertib and ipatasertib are already under way in HR+ and triple-negative breast cancer. While the identification of predictive biomarkers of response and resistance to AKT inhibition represents an unmet need, new combination strategies are under investigation aiming to boost the therapeutic efficacy of these drugs. As such, trials combining capivasertib and ipatasertib with CDK4/6 inhibitors, immune checkpoint inhibitors, and PARP inhibitors are currently ongoing. This review summarizes the available evidence on AKT inhibition in breast cancer, reporting both efficacy and toxicity data from clinical trials along with the available translational correlates and then focusing on the potential use of these drugs in new combination strategies.

Martorana|Federica|F|
Motta|Gianmarco|G|
Pavone|Giuliana|G|
Motta|Lucia|L|
Stella|Stefania|S|
Vitale|Silvia Rita|SR|
Manzella|Livia|L|
Vigneri|Paolo|P|

AKT inhibitors
breast cancer
clinical trials
PI3K/AKT/mTOR pathway
targeted therapy


Anatomical pathways involved in generating and sensing rhythmic whisker movements.

Abstract: The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception.

Bosman|Laurens W J|LW|
Houweling|Arthur R|AR|
Owens|Cullen B|CB|
Tanke|Nouk|N|
Shevchouk|Olesya T|OT|
Rahmati|Negah|N|
Teunissen|Wouter H T|WH|
Ju|Chiheng|C|
Gong|Wei|W|
Koekkoek|Sebastiaan K E|SK|
De Zeeuw|Chris I|CI|

sensorimotor integration
barrel cortex
anatomy
cerebellum
basal ganglia
follicle–sinus complex
rhythmic movements
vibrissa


Scattered accumulation hotspots of macro-litter on the seafloor: Insights for mitigation actions.

Abstract: Marine litter is an ever-increasing problem that demands immediate reduction plans and mitigation actions that should act synergically to efficiently meet ambitious goals. Since the seafloor has been recognized as the major sink for marine debris, the study of litter accumulation dynamics represent a fundamental tool to evaluate possible removal actions. We analysed a 7 years (2013-2019) standardized data series collected along Sardinian fishing grounds through MEDiterranean International Trawl Survey, for which estimates of density and weight of seafloor macro-litter were calculated for over 707 hauls. Results show the absence of any temporal trend in seafloor macro-litter density and weight, but rather indicate a spatial and bathymetric segregation of different litter categories. Our data showed how different sources and physical features of macro-litter items (i.e., plastic and fishing gear, rubber, glass, metals, and cloth) led to spatially segregated accumulation hotspots. We also point out here how the identification of seafloor macro-litter hotspots using aggregated data that include plastic items could obscure the identification of other segregated but yet relevant hotspots of other macro-litter categories accumulated in the marine environment. These hotspots often occurred at shallower depths and closer to coastlines, thus representing potential spots where eventual future litter removal action could be prioritized.

Cau|Alessandro|A|
Franceschini|Simone|S|
Moccia|Davide|D|
Gorule|Pankaj A|PA|
Agus|Blondine|B|
Bellodi|Andrea|A|
Cannas|Rita|R|
Carugati|Laura|L|
Cuccu|Danila|D|
Dessì|Claudia|C|
Marongiu|Martina F|MF|
Melis|Riccardo|R|
Mulas|Antonello|A|
Porceddu|Riccardo|R|
Porcu|Cristina|C|
Russo|Tommaso|T|
Follesa|Maria Cristina|MC|

Marine litter
Litter removal
Mitigation strategies
Seafloor macrolitter hotspots
Single-use plastic


Romidepsin hepatocellular carcinoma suppression in mice is associated with deregulated gene expression of bone morphogenetic protein and Notch signaling pathway components.

Abstract: Recently, our group showed that Romidepsin, a histone deacetylase inhibitor (HDACi), suppressed diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in mice. In the present study, we investigated the effect of Romidepsin-treatment on gene expression levels of components of Bmp and Notch signaling pathways, which are both known to be aberrantly regulated in hepatocarcinogenesis. Total RNA from liver tissue samples and paraffin-embedded livers were retrieved from a recent experiment where C57BL/6 mice were treated with Romidepsin 10 months after DEN challenge and sacrificed 2 months later. RT qPCR was used for quantification of gene expression and immunohistochemistry for in situ protein detection. Regarding Bmp pathway, Romidepsin HCC-suppression was found to correlate significantly with Bmp2 and Bmp7 ligand up- and down-regulation, respectively. Intracellularly, Romidepsin-treated HCC mice exhibited a significant elevation of Bmp-inhibitor Smurf2 and Bmp-target gene Id3, as compared to the HCC untreated controls. Concerning Notch signaling, higher expression levels of ligands Jag1/Dll4, accompanied by a decreased expression of receptor Notch2, were identified in the Romidepsin-treated group. Τhe anti-oncogenic effect of Romidepsin, also correlated significantly with an increased expression of Hes1 target, as well as an up- and down-regulation of Klf4 and Sox9 transcription factors, respectively. Moreover, the cancer-related genes Snai2 and p21, known to be involved in many signaling pathways, including Bmp and Notch, were also found to be downregulated in Romidepsin-treated mice. Romidepsin HCC suppression is associated with gene expression deregulation of selective components of both Bmp and Notch signaling cascades.

D015972:Gene Expression Regulation, Neoplastic

Romidepsin
Notch
Histone deacetylase inhibitors (HDACi)
Hepatocellular carcinoma (HCC)
Bone morphogenetic proteins (Bmp)
Diethylnitrosamine (DEN)


Outcomes of a Suicide Prevention Gatekeeper Training Program Among School Personnel.

Abstract:
BACKGROUND
Gatekeeper suicide prevention programs train staff to increase the identification and referral of suicidal individuals to the appropriate resources.

AIMS
We evaluated Act on FACTS: Making Educators Partners in Youth Suicide Prevention (MEP), which is an online training program designed to enhance the knowledge of suicide risk factors and warning signs as well as improve participants' attitudes and self-efficacy/confidence.

METHOD
School personnel (N = 700) completed a survey administered before and immediately after the training to assess gains in training outcomes and to evaluate participants' satisfaction with the training.

RESULTS
Results indicated that MEP participants demonstrated significant increases in suicide knowledge, attitudes, and self-efficacy. Moreover, exploratory analyses revealed moderating effects of professional role on pre-/posttest changes in self-efficacy, but not suicide knowledge or attitudes. Specifically, guidance counselors demonstrated significantly smaller increases in self-efficacy/confidence compared with teachers and classroom aids, whereas teachers demonstrated significantly larger increases in self-efficacy/confidence compared with administrators. The majority of school personnel who completed the MEP program were satisfied with the training content and experience.

CONCLUSION
Although the current findings are promising, more rigorous evaluations employing randomized controlled research designs are warranted to adequately determine the effectiveness of the MEP program.

Lamis|Dorian A|DA|
Underwood|Maureen|M|
D'Amore|Nicole|N|

suicide prevention
gatekeeper training
school personnel
youth


Factually based autism awareness campaigns may not always be effective in changing attitudes towards autism: Evidence from British and South Korean nursing students.

Abstract: This study explored the relationship between autism knowledge, autistic traits, frequency of contact with autistic people and attitudes towards these individuals in British and South Korean student nurses and whether these relationships were affected by the presence of autistic traits. In total, 331 participants (156 South Korean and 175 British) completed self-report measures of autism knowledge, attitudes towards autistic people, frequency of contact with these individuals and autistic traits. Although British participants demonstrated greater knowledge and more favourable attitudes, significant knowledge gaps were noted in both groups. Among British participants, knowledge was found to be only a marginal predictor of attitudes, whereas neither knowledge nor frequency of contact were predictive of attitudes among South Korean participants. Contrary to previous research findings, cultural differences in the presence of autistic traits were not noted, nor were these traits found to be related to attitudes towards autistic people. The findings suggest that awareness initiatives which aim to address attitudes towards autism need more than simply increasing factual knowledge. More importantly, the results suggest that Western-developed autism awareness initiatives may be ineffectual if cultural differences are not considered.

D001290:Attitude
D000067877:Autism Spectrum Disorder
D001321:Autistic Disorder
D006801:Humans
D056910:Republic of Korea
D013338:Students, Nursing
D011795:Surveys and Questionnaires

attitudes
nurses
nursing students
knowledge
Autism Quotient
South Korea
broader autism phenotype
cross-cultural
healthcare professionals


Towards Truly Wearable Systems: Optimizing and Scaling Up Wearable Triboelectric Nanogenerators.

Abstract: Triboelectric nanogenerator (TENG) is an upcoming technology to harvest energy from ambient movements. A major focus herein is harvesting energy from human movements through wearable TENGs, which are constructed by integrating nanogenerators into clothing or accessories. Textile-based TENGs, which include fiber, yarn, and fabric-based TENG structures, account for the majority of wearable TENGs, with many designs and applications demonstrated recently. This calls for a comprehensive analysis of textile-based TENG technology, and how the state-of-the-art device optimization concepts can be deployed to construct them efficiently. Concurrently, how advanced engineering concepts and industrial manufacturing techniques, which are bound with fiber, yarn, and fabric-related developments, can be applied into the TENG context for their output enhancement is still under investigation. Herein, we fill this vital gap by analyzing the state-of-the-art developments, upcoming trends, output optimization strategies, scalability, and prospects of the textile-based TENG technology, presenting a textile engineering perspective.

Gunawardhana|K R Sanjaya D|KRSD|
Wanasekara|Nandula D|ND|
Dharmasena|R D Ishara G|RDIG|

Energy Resources
Materials Design
Nanostructure
Nanotechnology
Smart Textiles


Arylphosphonylation and arylazidation of activated alkenes.

Abstract: Two radical-mediated processes of activated alkenes, namely arylphosphonylation and arylazidation, are described. The difunctionalization of alkenes by a tandem process that involves radical addition, 1,4-aryl migration, and desulfonylation generates α-aryl-β-heterofunctionalized amides bearing a quaternary stereocenter when the substituent on the nitrogen atom is an aryl group. Alternatively, heterooxindoles or spirobicycles can be obtained with excellent regioselectivity in the presence of an alkyl substituent on the nitrogen atom.

alkenes
difunctionalization
radicals
desulfonylation
aryl migration


Evidence of biological activity of Mentha species extracts on apoptotic and autophagic targets on murine RAW264.7 and human U937 monocytic cells.

Abstract:
CONTEXT
Mints (Lamiaceae) are used as traditional remedies for the treatment of several diseases. Their extracts are recognized as anti-inflammatory compounds.

OBJECTIVE
This study characterized the cytotoxic effects of Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L). Huds (MR) on macrophage cells (RAW264.7; U937) and determined their impact on apoptosis and autophagy, which can play a role in controlling inflammation.

MATERIALS AND METHODS
The extracts were prepared in culture medium and tested from 25 to 400 μg/mL after 24-48 h of treatment. To show the effect of the aqueous ethanol (50%) extracts on apoptosis and authophagy, the presence of cleaved caspase-3, and the conversion of LC3-I to LC3-II was evaluated by Western blotting.

RESULTS
Compared with the MTT assay, crystal violet showed a pronounced decrease in the number of cells with all extracts at 48 h. Calculated IC50 values were 257.31, 207.82 and 368.02 μg/mL for MS, MP and MR, respectively. A significant increase in PI positive cells was observed with all extracts at 200-400 μg/mL. Mitochondrial dysfunctions and nuclear morphological changes were detected with MS and MR extracts at 400 μg/mL. At this concentration, no cleaved caspase-3 was found whereas stabilized caspase-3 in its dimeric form was identified. MS and MR extracts also favour LC3-I to LC3-II conversion which is a criterion of autophagy.

CONCLUSIONS
The cytotoxic profiles depend on the extracts considered; MS extract showed the strong activity. However, all the mint extracts studied interact with the apoptotic and autophagic pathways at elevated concentrations.

Brahmi|Fatiha|F| Hadj-Ahmed|Samia|S| Zarrouk|Amira|A| Bezine|Maryem|M| Nury|Thomas|T| Madani|Khodir|K| Chibane|Mohamed|M| Vejux|Anne|A| Andreoletti|Pierre|P| Boulekbache-Makhlouf|Lila|L| Lizard|Gérard|G|

Mentha spicata
mentha pulegium
mentha rotundifolia
mitochondria


Neonatal salmonella typhi meningitis: a rare entity.

Abstract: Salmonella meningitis is rarely seen in neonates and if it is present, it is associated with complications like subdural collections and abscesses. We are presenting a case of Salmonella meningitis in a 28 days old neonate who developed complications like extensive subdural collections and ventriculitis. The child responded well to prolonged systemic antibiotics and other supportive measures.

Singhal|Vikram|V| Ek|Saleem|S| Sm|Rajesh|R| Coutinho|Anita|A|


Development and evaluation of novel miltefosine-polyphenol co-loaded second generation nano-transfersomes for the topical treatment of cutaneous leishmaniasis.

Abstract: Objective: To test the hypothesis that miltefosine (MTF)-polyphenol co-loaded second-generation nano-transfersomes (SGNTs) can be an effective approach for the topical treatment of cutaneous leishmaniasis (CL).Methods: The co-loaded SGNTs with various MTF-polyphenol combinations were developed, evaluated and compared for the entrapment efficiency, vesicle size, deformability index, ex-vivo permeation, cytotoxicity, and anti-leishmanial potential, using both in-vitro and in-vivo models.Results: The co-loaded SGNTs were spherical in shape, with an average size of 119 ± 1.5 nm and a high entrapment efficiency of 73.7 ± 3.7%. The ex-vivo study displayed a 3.2-fold higher permeation of MTF when entrapped in co-loaded SGNTs, whereas cytotoxicity potential of co-loaded SGNTs was 43.2% higher than the MTF solution. A synergistic interaction was observed between MTF and apigenin (APG) among all polyphenols and an 8.0-fold lower IC50 was found against amastigotes of DsRed Leishmania mexicana, compared with the plain MTF solution. Moreover, the in-vivo studies displayed a 9.5-fold reduced parasitic burden in the L. mexicana infected BALB/c mice treated with MTF-APG co-loaded SGNTs gel.Conclusions: The potential of MTF-APG co-loaded SGNTs topical formulation is established for the first time as an effective drug delivery strategy against CL.

Dar|M Junaid|MJ|0000-0003-0210-4412
McElroy|Craig A|CA|
Khan|Muhammad Ijaz|MI|
Satoskar|Abhay R|AR|
Khan|Gul Majid|GM|0000-0003-3282-1711

D002851:Chromatography, High Pressure Liquid


Epistemological and methodological paradoxes: secondary care specialists and their challenges working with adolescents with medically unexplained symptoms.

Abstract:
Background
Early adolescence is considered a critical period for the development of chronic and recurrent medically unexplained symptoms (MUS), and referrals and system-initiated patient trajectories often lead to an excess of examinations and hospitalizations in the cross-section between mental and somatic specialist care for this group of patients. Dimensions of the relationship and communication between clinician and patient are shown in primary care studies to be decisive for subsequent illness pathways, often creating adverse effects, but knowledge on clinical communication in specialist care is still scarce.

Methods
This study explores communicative challenges specific to clinical encounters between health professionals and adolescent patients in specialist care, as presented through interviews and focus group data with highly experienced specialists working in adolescent and child services at a Norwegian university hospital.

Results
The results are presented in a conceptual model describing the epistemological and methodological paradoxes inherent in the clinical uncertainty of MUS. Within these paradoxes, the professionals try to solve the dilemmas by being creative in their communication strategies; applying metaphors and other rhetorical devices to explain complex ideas; creating clinical prototypes as a way to explain symptoms and guide them in clinical action; relying on principles from patient-centered care involving empathy; and trying to balance expertise and humility.

Conclusion
The challenges in communication arise as a result of opposing discourses on biomedicine, family, health and adolescence that create dilemmas in everyday clinical work. By moving away from a positivist and biomedical framework towards an interpretive paradigm, where culturally derived and historically situated interpretations are used to understand the social life-world of the patient, one can create a more humane health service in accordance with ideals of patient-centered care.

Adolescents
Medically unexplained symptoms
Specialist care
Communication
Clinical encounters