Prognostic Nomogram for Overall Survival in Extranodal Natural Killer/T-Cell Lymphoma Patients.

Abstract:
BACKGROUND
Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare lymphoid malignancy with diverse clinical features and prognoses. The aims of this study were to explore the pretreatment prognostic factors of ENKTL and develop a new individual prognostic model.

PATIENTS AND METHODS
We retrospectively enrolled 81 ENKTL patients with newly diagnosed disease between June 2006 and August 2017 at the Affiliated Cancer Hospital of Guangxi Medical University. Survival analysis was used to assess the prognostic value of various factors. A nomogram was developed to predict overall survival (OS) based on the Cox proportional hazards model.

RESULTS
The median survival time of the patients was 48 months, and the 5-year OS rate was 47.5%. Cox regression analysis showed that the prognostic factors of OS for ENKTL patients included Eastern Cooperative Oncology Group performance status, Ann Arbor stage, pretreatment albumin-to-globulin ratio, and platelet count. A prognostic nomogram was developed to predict the OS rate for ENKTL patients based on these factors. The calibration curve showed that the nomogram was able to predict OS accurately. The concordance index of the nomogram for OS prediction was 0.807.

CONCLUSION
Our proposed nomogram based on Eastern Cooperative Oncology Group performance status, Ann Arbor stage, albumin-to-globulin ratio, and platelet count provides an individualized risk estimate of OS in patients with ENKTL.

Li|Kaiguo|K| Wang|Ruyue|R| Huang|Shiting|S| Pan|Xinbin|X| Chen|Hongmin|H| Zhou|Lei|L| Wei|Junbao|J| Wu|Chunhua|C| Zhu|Xiaodong|X| Liang|Shixiong|S| Qu|Song|S|

Lymphoid malignancy
Prognostic model
Albumin-to-globulin ratio
Platelet count
Calibration curve


First-line tyrosine kinase inhibitors in metastatic renal cell carcinoma: A regional cancer center experience.

Abstract:
BACKGROUND
Renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy, and historically a poor prognosis for metastatic disease has been reported, with a 5-year survival rate of <10%. Significant advances have been made in the last decade since the introduction of different tyrosine kinase inhibitors (TKIs) such as sunitinib, pazopanib, and sorafenib. Unfortunately, even though the TKIs have been used for a long time, there are very few published data regarding the experience of TKI therapy in metastatic RCC (mRCC) from India.

MATERIALS AND METHODS
This is a single institutional review of mRCC patients treated between January 2012 and July 2017. Patients who received at least 1 month of first-line TKIs were included for analysis of response rates, toxicity, survival outcomes, and prognostic factors.

RESULTS
Of the 40 mRCC patients, 31 (77.5%) were males. Median age at diagnosis was 58 years (range: 38-80 years). The most common site of metastasis was lungs (n = 24) followed by bone (n = 19) and liver (n = 7). Three patients had favorable risk disease, whereas 25 had intermediate risk and 12 had poor risk disease according to the MSKCC risk criteria. First-line TKI therapy used was sunitinib in 24, pazopanib in 11, and sorafenib in 5 patients. Toxicities of TKIs were Grade 1 or 2 in 13 patients and Grade 3 or 4 in 9 patients; the most common being fatigue, followed by hand-foot syndrome, skin rash, mucositis, and hypertension. Overall, 29 patients (72.5%) had disease control (complete responses in 1, partial responses in 10, and stable disease in 18 patients), whereas 11 had progression of disease at initial evaluation. At a median follow-up of 16 months (range: 2-38 months), median progression-free survival (PFS) was 10.8 months and median overall survival was 19.1 months.

CONCLUSIONS
Sunitinib and pazopanib are viable first-line options for mRCC and showed a comparable PFS in Indian patients. Careful patient selection, tailoring of TKI doses, and careful toxicity management are essential for optimum therapy.

Rudresha|A H|AH|
Chaudhuri|Tamojit|T|
Lakshmaiah|K C|KC|
Babu|Govind K|GK|
Lokanatha|D|D|
Jacob|Linu Abraham|LA|
Suresh Babu|M C|MC|
Lokesh|K N|KN|
Rajeev|L K|LK|

D064420:Drug-Related Side Effects and Adverse Reactions

Metastatic renal cell carcinoma
sunitinib
pazopanib
sorafenib


Action mechanisms of Onabotulinum toxin-A: hints for selection of eligible patients.

Abstract: In the past few decades, the so-feared botulinum toxin has conversely acquired the role of a ever more versatile therapeutic substance, used in an increasing number of pathological situations, including chronic headache and more precisely in the prophylaxis of chronic migraine. The medical use of botulinum toxin allowed to better understand its multiple mechanisms of action. Investigations about the pathophysiology of primary and secondary headaches has shown a series of common biological elements that frequently are also targets of the action of botulinum toxin. These increasing evidences allowed to identify some biochemical, neurophysiological and radiological markers that may be useful in the individuation of patients which probably will respond to the treatment with Onabotulinum toxin-A among chronic migraineurs. These predictors include CGRP plasmatic levels, specific laser-evoked potential responses, peculiar brain MRI and fMRI and characteristic clinical manifestations. Unfortunately, at now, these predictors are still not available for the clinical practice. Furthermore, the better knowledge about biology of headaches and regarding botulinum toxin activities may also help in directing investigations on the possible use of Onabotulinum toxin-A in other headaches different from migraine. This review tries to show in detail these biological mechanisms and their implication in selecting patients eligible for the treatment with Onabotulinum toxin-A.

Onabotulinum toxin-A
Headache
Migraine
CGRP
TRP


Malaria, tuberculosis and HIV: what's new? Contribution of the Institut Hospitalo-Universitaire Méditerranée Infection in updated data.

Abstract: The Institut Hospitalo-Universitaire Méditerranée Infection is positioned for the diagnosis, prevention and treatment of the 'big three' killer diseases: malaria, tuberculosis and HIV. We implemented the use of new diagnostic samples such as stools and new diagnostic tests such as mass spectrometry for the dual identification of vectors and pathogens. Furthermore, advances in the prevention and treatment of malaria and tuberculosis are reviewed, along with advances in the understanding of the role of microbiota in the resistance to HIV infection. These achievements represent a major step towards a better management of the 'big three' diseases worldwide.

Almeras|Lionel|L|
Basco|Leonardo K|LK|
Sokhna|Cheikh|C|
Ranque|Stéphane|S|
Parola|Philippe|P|
Devaux|Christian|C|
Brouqui|Philippe|P|
Drancourt|Michel|M|
Pradines|Bruno|B|

malaria
tuberculosis
HIV
Diagnostic
vector
microbiota
resistance
Mycobacterium tuberculosis
Plasmodium falciparum
drugs


Upper airway structural changes induced by CPAP in OSAS patients: a study using drug-induced sleep endoscopy.

Abstract: We studied upper airway structural changes induced by continuous positive airway pressure (CPAP) in obstructive sleep apnea syndrome (OSAS) patients using drug-induced sleep endoscopy (DISE). This prospective study was conducted at an academic secondary referral center. In total, 28 male OSAS patients (mean age 41.1 years) with only retropalatal level obstructions were enrolled. Measurements of the obstruction site were obtained in two steps: first a measurement was taken of the obstruction site in accordance with sleep apnea, then, a measurement was taken of the obstruction site in accordance with DISE-assisted CPAP titration, including quantitative changes in the occlusion site before and after CPAP in pixel format using an area calculation program. There was a tendency for persistent closing in cases of antero-posterior (AP) obstruction versus cases of lateral (Lat) obstruction in the CPAP titration. Lat obstructions showed a tendency to be wider than AP obstructions in the quantitative analysis. These results show that the pattern and degree of airway expansion after CPAP differ in accordance with the obstruction site.

Jung|Sung Hoon|SH|
Koo|Soo Kweon|SK|
Choi|Jang Won|JW|
Moon|Ji Seung|JS|
Lee|Sang Hoon|SH|

D045422:Continuous Positive Airway Pressure

Continuous positive airway pressure
Sleep apnea syndrome
Quantitative analysis


Upregulated miR-410 is linked to poor prognosis in colorectal cancer.

Abstract:
BACKGROUND
Although miR-410 acts as a cancer inducer in colorectal cancer, there is limited data on the clinical implications of miR-410 expression levels in patients. We hypothesized a link between miR-410 expression and its potential clinical values in patients with colorectal cancer.

MATERIAL AND METHODS
120 colorectal cancer tissue specimens and 120 adjacent non-tumour tissues were obtained. Quantification of miR-410 expression levels was determined by, quantitative RT-PCR. Expression was analysed by clinical features.

RESULTS
miR-410 was up-regulated in malignant tissues compared with corresponding normal tissues (P < 0.01), with TNM stage and lymph node metastasis (P = 0.03, P = 0.004, respectively), and with worse overall survival (P = 0.002). Multivariate survival analysis identified it as an independent risk factor for outcome (P = 0.021, HR = 2.19; 95% CI = 1.12-4.25).

CONCLUSION
Compared to normal non-cancerous tissues, miR-410 was overexpressed in tumour tissues and is independently associated with the unfavourable outcome. Levels of MiR-410 might a useful laboratory tool in managing and predicting the prognosis of colorectal cancer.

D015972:Gene Expression Regulation, Neoplastic

D060888:Real-Time Polymerase Chain Reaction

miR-410
prognosis
Colorectal cancer
overall survival
RT-qPCR
clinicopathological characteristics


Emotional variables, dropout and academic performance in Spanish nursing students.

Abstract: The dropout of university studies is a main concern in many countries, also for Health Sciences degrees. The reviews on dropout in all university degrees as well as nursing generally show multidimensional causes with factors related both to institutional and students' characteristics. Regarding the personal variables of students, researchers have focused on financial, family and personality features. Far less attention has been devoted to emotional variables. This study aims to explore whether individual variables of the emotional domain such as perceived emotional intelligence, dispositional optimism/pessimism and depressive rumination are related and/or can predict students' intention to dropout and academic performance. Using a cross-correlational approach, data were obtained from a sample of 144 nursing students. Students with a pessimistic disposition revealed a greater tendency to drop out. The remaining variables correlated significantly with pessimism but had no predictive value on dropout. Our results suggest that students with low levels of emotional clarity and repair and high depressive rumination have pessimistic expectations, so they are more likely to leave studies. No significant results were found in relation to academic performance. We conclude with an identification of strategies to increase retention and academic success.

Roso-Bas|Fátima|F|
Pades Jiménez|Antonia|A|
García-Buades|Esther|E|

Academic performance
Emotional intelligence
Dispositional optimism/pessimism
Rumination
Student dropout


Binding of a proline-independent hydrophobic motif by the Candida albicans Rvs167-3 SH3 domain.

Abstract: Src-homology 3 (SH3) domains are small protein-protein interaction modules. While most SH3 domains bind to proline-x-x-proline (PxxP) containing motifs in their binding partners, some SH3 domains recognize motifs other than proline-based sequences. Recently, we showed that the SH3 domain of Candida albicans Rvs167-3 binds peptides enriched in hydrophobic residues and containing a single proline residue (RΦxΦxΦP, where x is any amino acid and Φ is a hydrophobic residue). Here, we demonstrate that the proline in this motif is not required for Rvs167-3 SH3 recognition. Through mutagenesis studies we show that binding of the peptide ligand involves the conserved tryptophan in the canonical PxxP binding pocket as well as residues in the extended n-Src loop of Rvs167-3 SH3. Our studies establish a novel, proline-independent, binding sequence for Rvs167-3 SH3 (RΦxΦxΦ) that is comprised of a positively charged residue (arginine) and three hydrophobic residues.

Gkourtsa|Areti|A|
van den Burg|Janny|J|
Avula|Teja|T|
Hochstenbach|Frans|F|
Distel|Ben|B|

D000595:Amino Acid Sequence
D002176:Candida albicans
D004252:DNA Mutational Analysis
D005656:Fungal Proteins
D008958:Models, Molecular
D008969:Molecular Sequence Data
D011392:Proline
D011485:Protein Binding
D011487:Protein Conformation
D014364:Tryptophan
D018909:src Homology Domains

Candida albicans
Rvs167-3
SH3 domain
Non-canonical ligand
Proline-independent binding


Defined conjugation of glycans to the lysines of CRM197 guided by their reactivity mapping.

Abstract: Systematic characterisation of the reactivity of the lysine moieties in CRM197 towards N-hydroxysuccinimide linkers bearing alkynes or azides is described. This involves two-step conjugation of various glycans to CRM197 by click chemistry in a well-defined manner. By semiquantitative LC-MS/MS analysis of proteolytic digests of the conjugates formed, the reactivity of lysine residues in the protein was mapped and ranked. Computational analysis of the solvent accessibility of each lysine residue (based on the CRM197 crystal structure) established a correlation between reactivity and surface exposure. By this approach, conjugation involving lysine residues (normally a random process) can be controlled. It enables the preparation of lysine-mediated glycoconjugates with improved batch-to-batch reproducibility, thereby producing neo-glycoconjugates with more-consistent biological activity.

Crotti|Stefano|S| Zhai|Huili|H| Zhou|Jing|J| Allan|Martin|M| Proietti|Daniela|D| Pansegrau|Werner|W| Hu|Qi-Ying|QY| Berti|Francesco|F| Adamo|Roberto|R|

D002851:Chromatography, High Pressure Liquid

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

glycoconjugates
bioconjugation
carbohydrates
mass spectrometry
vaccines


Feasibility of low-dose digital subtraction angiography protocols for the endovascular treatment of intracranial dural arteriovenous fistulas.

Abstract:
BACKGROUND
Among neurointerventional procedures, the embolization of complex shunt lesions usually requires more radiation dose. We aimed to evaluate the procedural outcome and safety in using low-dose DSA protocols for intracranial dural arteriovenous fistula (AVF) embolization treatment.

METHODS
Between January 2014 and July 2018, 55 patients with dural AVFs who underwent endovascular treatment were included in the study. The low-dose group (n = 27) included from January 2016 used various low-dose DSA protocols made by modifying the thickness of the copper filter or the detector entrance dose. We compared radiation dose metrics, such as air-kerma, kerma-air product (KAP), and fluoroscopy time, as well as clinical and imaging outcomes with the conventional-dose group (n = 28) included before January 2016.

RESULTS
The total KAP was 40.1% lower in the low-dose group (87.9 vs. 146.7 Gy cm2, p = 0.002). The average number of DSA runs (25.1 vs. 25.5, p = 0.86) and fluoroscopy times (77.4 vs. 69.7 min, p = 0.48) were similar between the groups. An immediate favorable occlusion rate (total or near total occlusion) was achieved in 41 (74.5%) patients. Ten patients (18.2%) underwent additional procedures due to residual (n = 6) and/or recurrent (n = 5) lesions. At a median of 10 months follow-up, 45 patients (86.5%) had achieved favorable occlusion. Treatment outcomes showed no significant between-group differences. There was one case (1.8%) of procedure-related complications in the low-dose group. All but one patient showed favorable clinical outcomes (modified Rankin score ≤ 2).

CONCLUSION
The low-dose protocols were feasible by showing significant radiation dose reduction and acceptable procedural outcome.

D020785:Central Nervous System Vascular Malformations

Angiography
Intervention
Standards
Technique
Vascular malformation


The reliability of a novel magnetic resonance imaging-based tool for the evaluation of forefoot bursae in patients with rheumatoid arthritis: the FFB score.

Abstract:
OBJECTIVE
The aim of this study was to determine the reliability of an MRI-based score that evaluates forefoot bursae (FFBs) in patients with RA.

METHODS
Items for inclusion, grading criteria and MRI sequences were determined iteratively. The score was evaluated in 30 patients with established RA. Reader agreement was evaluated using the percentage of exact/close agreement, Bland-Altman plots, kappa and intraclass correlation coefficient analyses.

RESULTS
The FFB score assesses nine forefoot regions and contains four items: presence, shape, enhancement and magnetic resonance characteristics. The FFB score showed moderate to good intra- and interreader agreement (κ range = 0.5-0.9 and 0.47-0.87, respectively).

CONCLUSION
The FFB score is adequately reliable in the evaluation of bursa-like lesions of the forefoot in patients with RA.

Cherry|Lindsey|L|
King|Leonard|L|
Thomas|Matthew|M|
Roemer|Frank|F|
Culliford|David|D|
Bowen|Catherine J|CJ|
Arden|Nigel K|NK|
Edwards|Christopher J|CJ|

D000293:Adolescent
D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D001172:Arthritis, Rheumatoid
D002061:Bursa, Synovial
D003430:Cross-Sectional Studies
D018450:Disease Progression
D005260:Female
D005500:Follow-Up Studies
D005545:Forefoot, Human
D006801:Humans
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D015203:Reproducibility of Results
D012720:Severity of Illness Index
D055815:Young Adult

rheumatoid arthritis
disease activity
foot
inflammation
magnetic resonance imaging
outcome measures
radiology
synovium


Development and Validation of CAGIB Score for Evaluating the Prognosis of Cirrhosis with Acute Gastrointestinal Bleeding: A Retrospective Multicenter Study.

Abstract:
INTRODUCTION
Acute gastrointestinal bleeding (GIB) is a major cause of death in liver cirrhosis. This multicenter study aims to develop and validate a novel and easy-to-access model for predicting the prognosis of patients with cirrhosis and acute GIB.

METHODS
Patients with cirrhosis and acute GIB were enrolled and randomly divided into the training (n = 865) and validation (n = 817) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses, and then a new prognostic model (i.e., CAGIB score) was established. Area under curve (AUC) of CAGIB score was calculated by receiver operating characteristic curve analysis and compared with Child-Pugh, model for end-stage liver disease (MELD), MELD-Na, and neutrophil-lymphocyte ratio (NLR) scores.

RESULTS
In the training cohort, hepatocellular carcinoma (HCC), diabetes, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and serum creatinine (Scr) were independent predictors of in-hospital death. CAGIB score = diabetes (yes = 1, no = 0) × 1.040 + HCC (yes = 1, no = 0) × 0.974 + TBIL (μmol/L) × 0.005 - ALB (g/L) × 0.091 + ALT (U/L) × 0.001 + Scr (μmol/L) × 0.012 - 3.964. In the training cohort, the AUC of CAGIB score for predicting in-hospital death was 0.829 (95% CI 0.801-0.854, P < 0.0001), which was higher than that of Child-Pugh (0.762, 95% CI 0.732-0.791), MELD (0.778, 95% CI 0.748-0.806), MELD-Na (0.765, 95% CI 0.735-0.793), and NLR (0.587, 95% CI 0.553-0.620) scores. In the validation cohort, the AUC of CAGIB score (0.714, 95% CI 0.682-0.746, P = 0.0006) remained higher than that of Child-Pugh (0.693, 95% CI 0.659-0.725), MELD (0.662, 95% CI 0.627-0.695), MELD-Na (0.660, 95% CI 0.626-0.694), and NLR (0.538, 95% CI 0.503-0.574) scores.

CONCLUSION
CAGIB score has a good predictive performance for prognosis of patients with cirrhosis and acute GIB.

Bai|Zhaohui|Z| Li|Bimin|B| Lin|Su|S| Liu|Bang|B| Li|Yiling|Y| Zhu|Qiang|Q| Wu|Yunhai|Y| Yang|Yida|Y| Tang|Shanhong|S| Meng|Fanping|F| Chen|Yu|Y| Yuan|Shanshan|S| Shao|Lichun|L| Qi|Xingshun|X|0000-0002-9448-6739

Prognosis
Cirrhosis
Gastrointestinal bleeding
MELD
Child–Pugh


The association between menarche, intensity of training and passive joint ROM in young pre-professional female dancers: A longitudinal follow-up study.

Abstract:
OBJECTIVES
To determine the association between the status of menarche (yes/no), the intensity of training and the potential to improve passive joint range of motion (ROM) over a 12-month period of dance training.

DESIGN
Prospective cohort study.

SETTING
Dance studio.

PARTICIPANTS
Fifty-nine female dancers aged 12.8 ± 0.5.

MAIN OUTCOME MEASURES
The dancers were asked about their dance intensity and screened for anthropometric parameters and passive joint ROM in Grades 7 and 8.

RESULTS
Along the 12 months of dance training, we found significantly increased ankle-foot en-pointe, hip abduction, and hip external rotation (ER); significantly decreased hip internal rotation (IR); and significant increased hip ER:IR ratio. In Grade 7, 26 dancers (44.1%) reached menarche (Yes menarche); in Grade 8 an additional 23 dancers (39.0%) reached menarche (No/Yes menarche); and 10 dancers (16.9%) had not reached menarche (No menarche). MANOVA (mixed models) with repeated measures to compare joint ROM between the three menarche groups (Yes; No/Yes; No), with h/week dance practice as a co-variant, showed that hip ER, ankle-foot en-pointe, and ER:IR were significantly correlated with h/week in all three menarche groups.

CONCLUSIONS
Most passive joint ROM can be improved over 12 months of dancing around the age onset of menarche. H/week of dance practice is a main factor contributing to improved hip ER, ankle-foot en-pointe and ER/IR ratio.

Steinberg|Nili|N| Tenenbaum|Shay|S| Stern|Myriam|M| Zeev|Aviva|A| Siev-Ner|Itzhak|I|

Passive joint ROM
Dancer
Dance intensity
Age onset of menarche


Optimising the introduction of multiple childhood vaccines in Japan: A model proposing the introduction sequence achieving the highest health gains.

Abstract:
BACKGROUND
Many countries struggle with the prioritisation of introducing new vaccines because of budget limitations and lack of focus on public health goals. A model has been developed that defines how specific health goals can be optimised through immunisation within vaccination budget constraints.

METHODS
Japan, as a country example, could introduce 4 new pediatric vaccines targeting influenza, rotavirus, pneumococcal disease and mumps with known burden of disease, vaccine efficacies and maximum achievable coverages. Operating under budget constraints, the Portfolio-model for the Management of Vaccines (PMV) identifies the optimal vaccine ranking and combination for achieving the maximum QALY gain over a period of 10 calendar years in children <5 years old. This vaccine strategy, of interest and helpful for a healthcare decision maker, is compared with an unranked vaccine selection process.

RESULTS
Results indicate that the maximum QALY gain with a fixed annual vaccination budget of 500 billion Japanese Yen over a 10-year period is 72,288 QALYs using the optimal sequence of vaccine introduction (mumps [1st], followed by influenza [2nd], rotavirus [3rd], and pneumococcal [4th]). With exactly the same budget but without vaccine ranking, the total QALY gain can be 20% lower.

CONCLUSION
The PMV model could be a helpful tool for decision makers in those environments with limited budget where vaccines have to be selected for trying to optimise specific health goals.

Standaert|Baudouin|B|
Schecroun|Nadia|N|
Ethgen|Olivier|O|
Topachevskyi|Oleksandr|O|
Morioka|Yoriko|Y|
Van Vlaenderen|Ilse|I|

Vaccine
Japan
Budget
Infectious diseases
Objective function
Optimisation model
Portfolio


Feasibility of standardized methods to specify behavioral pediatric obesity prevention interventions.

Abstract: Standardized methods are needed to evaluate what occurs within the 'black box' of behavioral interventions to prevent pediatric obesity. The purpose of this research is to evaluate methods to specify the behavior change techniques used and the amount of time spent discussing target weight-related behaviors in an intervention for parents of children at risk for becoming overweight or obese. Independent coders were trained to identify behavior change techniques and time spent discussing weight-related behaviors in audio recordings and transcripts of intervention sessions from 100 randomly selected participants. The behavior change technique taxonomy (BCTTv1) was used to code techniques present in sessions. A newly-developed tool was used to code time spent discussing each target weight-related behavior (e.g., physical activity, screen time). Sessions from a subset of these participants (N = 20) were double coded to evaluate inter-rater reliability. After revisions to coding protocols, coders reliably coded behavior change techniques used and time spent discussing target weight-related behaviors in sessions from the subset of 20 participants. The most commonly discussed target weight-related behavior was physical activity followed by energy intake and fruit and vegetable intake. On average, 13.9 (SD = 2.8) unique behavior change techniques were present across sessions for a given participant. These results offer reliable methods for systematically identifying behavior change techniques used and time spent discussing weight-related behaviors in a pediatric obesity prevention intervention. This work paves the way for future research to identify which specific target behaviors and techniques are most associated with the prevention of unhealthy weight gain in children.

JaKa|Meghan M|MM|
French|Simone A|SA|
Wolfson|Julian|J|
Jeffery|Robert W|RW|
Lorencatto|Fabianna|F|
Michie|Susan|S|
Langer|Shelby L|SL|
Levy|Rona L|RL|
Sherwood|Nancy E|NE|

Pediatric obesity
Behavior change techniques
Weight-related behaviors
Health behavior
Process evaluation


Decreased emotional reactivity of rats exposed to repeated phase shifts of light-dark cycle.

Abstract: Disturbed light-dark (LD) cycles are associated with circadian disruption of physiological and behavioural rhythms and in turn with an increased risk of disease development. However, direct causal links and underlying mechanisms leading to negative health consequences still need to be revealed. In the present study, we exposed male Wistar rats to repeated phase shifts of LD cycle and analysed their ability to cope with mild emotional stressors. In experiment 1, rats were submitted to either a regular 12:12 LD cycle (CTRL rats) or 8-h phase delay shifts applied every 2days for 5weeks (SHIFT rats). Subsequently, the behaviour was examined in the open-field, black-white box and elevated plus maze tests. In experiment 2, changes in blood pressure (BP), heart rate (HR) as well as the activity of autonomic nervous system were measured in telemeterised rats in response to open-field and black-white box tests before and after 5-week exposure to shifted LD regime. Locomotor activity was consistently higher in SHIFT than CTRL rats in in the open-field and black-white box tests. Interestingly, in the elevated plus maze, SHIFT rats displayed increased risk assessment and decreased grooming compared to CTRL rats. Anxiety measures were affected only in the black-white box, where SHIFT rats displayed reduced anxiety-like behaviour compared to CTRL rats. Differences in behavioural reactivity between SHIFT and CTRL rats did not correspond with BP and HR changes. However, exposure to phase shifts increased the sympathovagal reactivity in the black-white box. Together, our results demonstrated that disturbed LD conditions decreased emotional reactivity of rats and affected their ability to cope with emotional stressors denoting an additional risk mechanism linking disrupted circadian organisation to adverse health effects.

Behaviour
Cardiovascular system
Chronodisruption
Emotionality
Shift-work


Zwitterionic Polymer-Based Nanoparticles Encapsulated with Linalool for Regulating Central Nervous System.

Abstract: Aromatherapy is widely used in the treatment of diseases of the central nervous system, such as depression and anxiety. However, the rapid and uncontrolled release of aroma weakens the effects of aromatherapy. In this study, zwitterionic polymer-based nanoparticles encapsulated with linalool were prepared to improve the regulation of the central nervous system. First, the nanoparticles were modified with positive charges to adhere to the surface of silk via electrostatic interactions between the cationic nanoparticles and anionic silk. Besides, the fragrance was sustainably and controllably released from the nanoparticles. The effects of polymerization degree, polymer structure, and zeta potential on encapsulation efficiency, adhesion efficiency, and release profiles of linalool were then explored. The results showed that the linalool-encapsulated nanoparticles had the best performances of encapsulation, adhesion and release of fragrance when the polymerization degrees of hydrophilic block and hydrophobic block were 20 and 5, respectively. In addition, open field tests evaluated the regulation of nanoparticles on the central nervous system at the behavioral level. Measurements of dopamine, acetylcholine, and γ-aminobutyric acid expressions explored the mechanism of moderating effects on the central nervous system at the molecular level.

Lu|Zhiguo|Z| Zhang|Tianlu|T| Wang|Xiangyu|X| Wang|Jianze|J| Shen|Jie|J| Xiao|Zuobing|Z| Chen|Lei|L| Zhang|Xin|X|0000-0003-4106-0344

sustained and pH-sensitive release of fragrance


Incomer, a DD36E family of Tc1/mariner transposons newly discovered in animals.

Abstract:
Background
The Tc1/mariner superfamily might represent the most diverse and widely distributed group of DNA transposons. Several families have been identified; however, exploring the diversity of this superfamily and updating its classification is still ongoing in the life sciences.

Results
Here we identified a new family of Tc1/mariner transposons, named Incomer (IC), which is close to, but distinct from the known family DD34E/Tc1. ICs have a total length of about 1.2 kb, and harbor a single open reading frame encoding a ~ 346 amino acid transposase with a DD36E motif and flanked by short terminal inverted repeats (TIRs) (22-32 base pairs, bp). This family is absent from prokaryotes, and is mainly distributed among vertebrates (141 species of four classes), including Agnatha (one species of jawless fish), Actinopterygii (132 species of ray-finned fish), Amphibia (four species of frogs), and Mammalia (four species of bats), but have a restricted distribution in invertebrates (four species in Insecta and nine in Arachnida). All ICs in bats (Myotis lucifugus, Eptesicus fuscus, Myotis davidii, and Myotis brandtii) are present as truncated copies in these genomes, and most of them are flanked by relatively long TIRs (51-126 bp). High copy numbers of miniature inverted-repeat transposable elements (MITEs) derived from ICs were also identified in bat genomes. Phylogenetic analysis revealed that ICs are more closely related to DD34E/Tc1 than to other families of Tc1/mariner (e.g., DD34D/mariner and DD × D/pogo), and can be classified into four distinct clusters. The host and IC phylogenies and pairwise distance comparisons between RAG1 genes and all consensus sequences of ICs support the idea that multiple episodes of horizontal transfer (HT) of ICs have occurred in vertebrates. In addition, the discovery of intact transposases, perfect TIRs and target site duplications of ICs suggests that this family may still be active in Insecta, Arachnida, frogs, and fish.

Conclusions
Exploring the diversity of Tc1/mariner transposons and revealing their evolutionary profiles will help provide a better understanding of the evolution of DNA transposons and their impact on genomic evolution. Here, a newly discovered family (DD36E/Incomer) of Tc1/mariner transposons is described in animals. It displays a similar structural organization and close relationship with the known DD34E/Tc1 elements, but has a relatively narrow distribution, indicating that DD36E/IC might have originated from the DD34E/Tc1 family. Our data also support the hypothesis of horizontal transfer of IC in vertebrates, even invading one lineage of mammals (bats). This study expands our understanding of the diversity of Tc1/mariner transposons and updates the classification of this superfamily.

Sang|Yatong|Y| Gao|Bo|B| Diaby|Mohamed|M| Zong|Wencheng|W| Chen|Cai|C| Shen|Dan|D| Wang|Saisai|S| Wang|Yali|Y| Ivics|Zoltán|Z| Song|Chengyi|C|0000-0002-0488-4718

DD36E
Tc1/mariner transposons
Horizontal transfer


Can contamination of the environment by dioxins cause craniofacial defects?

Abstract: Cleft lip and cleft palate also known as orofacial cleft is a congenital malformation involving the partial or total lack of anatomical continuity of craniofacial tissue. The most common environmental factors that may cause orofacial clefts include pharmaceuticals, alcohol, addictive drugs, and tobacco smoke. Living in the area of industrial factories, garbage, ironworks, crematoria, wastewater treatment plants, and plastic waste landfills also has a significant impact on the development of the craniofacial defects. Some of the main factors causing the formation of congenital craniofacial defects are dioxins, of which emission to the environment is an important environmental and health problem. Dioxins are a diverse group of organic chemical compounds, derivatives of oxanthrene and fumarates, which are organoleptically imperceptible. Acting mainly through induction of inflammation, they influence a number of metabolic processes, including the process of bone mineralization and embryonic development. In this work, we highlight the problem of orofacial cleft including the impact of dioxin on development of this defect and the recommended prevention.

Dioxins
cleft lip
cleft palate
congenital malformations
prevention
environmental toxicology
pollution


Discharge to Inpatient Rehab Does Not Result in Improved Functional Outcomes Following Primary Total Knee Arthroplasty.

Abstract:
BACKGROUND
Monitored rehabilitation has long been considered an essential part of the recovery process in total knee arthroplasty (TKA). However, the optimal setting for rehabilitation remains uncertain. We sought to determine whether inpatient rehabilitation settings result in improved functional and patient-reported outcomes after primary TKA.

METHODS
All patients undergoing primary TKA from May 2007 to February 2011 were identified from our institutional total joint registry. Propensity score matching was then performed, resulting in a final cohort of 1213 matched pairs for discharge destination to either home or a rehabilitation facility (inpatient rehab or skilled nursing facility). Length of stay, need for manipulation, 6-month complications, and 2-year Western Ontario and McMaster Universities Osteoarthritis Index, Lower Extremity Activity Scale, 12-item Short Form Health Survey, and Hospital for Special Surgery knee expectations surveys were compared.

RESULTS
Patients discharged to a rehab facility were noted to have a shorter hospital length of stay (5.0 vs 5.4 days). Patients discharged to inpatient rehabilitation reported more fractures at 6 months postoperatively. However, no differences in manipulation rates, 2-year outcome scores, or changes in outcome scores were found between the 2 groups.

CONCLUSION
Inpatient rehabilitation settings did not result in lower complications at 6 months or improved functional or patient-reported outcomes at 2 years compared to discharge directly to home when patients are propensity matched for age, living situation, comorbidities, baseline functional status, and insurance status. This finding has important cost implications and calls into question whether the healthcare system should allow otherwise healthy patients to use inpatient rehabilitation services postoperatively after primary TKA.

Padgett|Douglas E|DE|
Christ|Alexander B|AB|
Joseph|Amethia D|AD|
Lee|You-Yu|YY|
Haas|Steven B|SB|
Lyman|Stephen|S|

D000071066:Patient Reported Outcome Measures

functional outcomes
primary total knee arthroplasty
rehabilitation
inpatient rehabilitation
discharge location


Theoretical study of proton coupled electron transfer reaction in the light state of the AppA BLUF photoreceptor.

Abstract: The BLUF (blue light sensor using flavin adenine dinucleotide) domain is widely studied as a prototype for proton coupled electron transfer (PCET) reactions in biological systems. In this work, the photo-induced concerted PCET reaction from the light state of the AppA BLUF domain is investigated. To model the simultaneous transfer of two protons in the reaction, two-dimensional potential energy surfaces for the double proton transfer are first calculated for the locally excited and charge transfer states, which are then used to obtain the vibrational wave function overlaps and the vibrational energy levels. Contributions to the PCET rate constant from each pair of vibronic states are then analyzed using the theory based on the Fermi's golden rule. We show that, the recently proposed light state structure of the BLUF domain with a tautomerized Gln63 residue is consistent with the concerted transfer of one electron and two protons. It is also found that, thermal fluctuations of the protein structure, especially the proton donor-acceptor distances, play an important role in determining the PCET reaction rate. © 2018 Wiley Periodicals, Inc.

Xu|Yang|Y|0000-0003-1414-4577 Bao|Peng|P| Song|Kai|K| Shi|Qiang|Q|

proton coupled electron transfer
AppA BLUF domain
Fermi's golden rule
QM/MM
molecular dynamics


Functional interaction of endoplasmic reticulum stress and hepatitis B virus in the pathogenesis of liver diseases.

Abstract: Hepatitis B virus (HBV) is a non-cytopathic virus that causes acute and chronic inflammatory liver diseases, often leading to the pathogenesis of hepatocellular carcinoma (HCC). Although many studies for the roles of HBV on pathogenesis of the liver diseases, such as non-alcoholic fatty liver disease (NAFLD), hepatic inflammation, cirrhosis, and HCC, have been reported, the mechanisms are not fully understood. Endoplasmic reticulum (ER) and mitochondria have the protective mechanisms to restore their damaged function by intrinsic or extrinsic stresses, but their chronic dysfunctions are associated with the pathogenesis of the various diseases. Furthermore, HBV can affect intra- or extracellular homeostasis through induction of ER and mitochondrial dysfunctions, leading to liver injury. Therefore, the mechanism by which HBV induces ER or mitochondrial stresses may be a therapeutic target for treatment of liver diseases.

Kim|So Young|SY|
Kyaw|Yi Yi|YY|
Cheong|Jaehun|J|

D000818:Animals
D000998:Antiviral Agents
D002908:Chronic Disease
D004195:Disease Models, Animal
D004721:Endoplasmic Reticulum
D059865:Endoplasmic Reticulum Stress
D006515:Hepatitis B virus
D006801:Humans
D008099:Liver
D008107:Liver Diseases
D008928:Mitochondria
D015398:Signal Transduction
D056811:Unfolded Protein Response
D053586:Virus Internalization
D014779:Virus Replication

Endoplasmic reticulum stress
Hepatitis B virus
Liver disease
Hepatitis B virus X protein
Unfolded protein response


Incise Draping Reduces the Rate of Contamination of the Surgical Site During Hip Surgery: A Prospective, Randomized Trial.

Abstract:
BACKGROUND
Iodophor-impregnated adhesive incise drapes are widely used during surgeries for reducing surgical site contamination. There is little evidence to support the latter belief. This study evaluated the efficacy of iodophor-impregnated adhesive drapes for reducing bacterial contamination and counts at the incision site during hip surgery.

METHODS
In this prospective, randomized clinical trial, we enrolled 101 patients undergoing open joint preservation procedure of the hip. Half the patients had the adhesive drape applied to the skin prior to incision, while the remainder underwent the same surgery without a drape. Culture swabs were taken from the surgical site at 5 points (preskin preparation, after skin preparation, postincision, before subcutaneous closure, prior to dressing application) and sent for culture and colony counts. Mixed-effects logistic regressions were used to estimate effects of time and drape application on contamination rate.

RESULTS
At the conclusion of surgery, 12.0% of incisions with adhesive drapes and 27.4% without adhesive drapes were positive for bacterial colonization. When controlling for preoperative colonization and other factors, patients without adhesive drapes were significantly more likely to have bacteria present at the time of skin closure, and at all time points when swab cultures were taken.

CONCLUSION
It appears that the iodophor-impregnated adhesive draping significantly reduces bacterial colonization of the incision. Bacterial count at the skin was extremely high in some patients in whom adhesive drapes were not used, raising the possibility that a subsequent surgical site infection or periprosthetic joint infection could arise had an implant been utilized.

Rezapoor|Maryam|M|
Tan|Timothy L|TL|
Maltenfort|Mitchell G|MG|
Parvizi|Javad|J|

hip surgery
iodophor-impregnated adhesive drapes
bacterial contamination
bacterial counts
surgical site infection


Synergistic effect of TiO2-CuWO4 on the photocatalytic degradation of atrazine.

Abstract: In this work, CuWO4 is prepared and its effect of improving photocatalytic degradation of atrazine by TiO2 as well as the synergetic mechanism is studied. Results show that the addition of CuWO4 (50 mg/L) into the reaction system can significantly enhance the efficiency of atrazine degradation, resulting in an increased degradation efficiency of 92.1% after 270 min, which is 1.94 times higher than that of the single TiO2. As the sintering temperate of CuWO4 was increased, the degradation efficiency of atrazine increased initially and then deceased after reaching a maximum at 500 °C. The origin of the synergistic effect of TiO2-CuWO4 is attributed to the introduction of solid CuWO4. The photochemical test results indicate that the photogenerated electrons transfer from irradiated TiO2 to CuWO4, which is beneficial to the O2 reduction and H2O2 formation in aqueous solution thus promoting the photocatalytic activity of TiO2. These observations unveil the importance of improving photocatalytic activity of TiO2 with Cu-bearing semiconductors.

Synergistic effect
Atrazine
CuWO4
Photocatalysis


The antioxidant activities effect of neutral and acidic polysaccharides from Epimedium acuminatum Franch. on Caenorhabditis elegans.

Abstract: A neutral polysaccharide (EAP-1N) and an acidic polysaccharide (EAP-2A) were purified from Epimedium acuminatum by DEAE-52 cellulose anion-exchange chromatography and gel-filtration chromatography. Their structures were characterized by chemical composition analysis, high-performance size exclusion chromatography (HPSEC), Fourier transform infrared spectrometry (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Further, their antioxidant activities were investigated both in vitro and in vivo. Results showed that EAP-2A had higher uronic acid content and larger average molecular weight than EAP-1N. Compared with EAP-1N, EAP-2A exhibited significantly scavenging activities against free radical in vitro, as well as strongly stimulating effect on antioxidant enzyme activities (including superoxide dismutases (SOD), catalases (CAT), and glutathione peroxidases (GSH-PX)) and preferably inhibitory effect on lipid peroxidation and protein carboxyl in the mode of Caenorhabditis elegans.

Xu|Zhou|Z| Feng|Shiling|S| Shen|Shian|S| Wang|Handong|H| Yuan|Ming|M| Liu|Jing|J| Huang|Yan|Y| Ding|Chunbang|C|

Antioxidant activities
Acidic polysaccharide
Epimedium acuminatum Franch
Caenorhabditis elegans
Neutral polysaccharide


Impact of the Noise Penalty Factor on Quantification in Bayesian Penalized Likelihood (Q.Clear) Reconstructions of 68Ga-PSMA PET/CT Scans.

Abstract: Functional imaging with 68Ga prostate-specific membrane antigen (PSMA) and positron emission tomography (PET) can fulfill an important role in treatment selection and adjustment in prostate cancer. This article focusses on quantitative assessment of 68Ga-PSMA-PET. The effect of various parameters on standardized uptake values (SUVs) is explored, and an optimal Bayesian penalized likelihood (BPL) reconstruction is suggested. PET acquisitions of two phantoms consisting of a background compartment and spheres with diameter 4 mm to 37 mm, both filled with solutions of 68Ga in water, were performed with a GE Discovery 710 PET/CT scanner. Recovery coefficients (RCs) in multiple reconstructions with varying noise penalty factors and acquisition times were determined and analyzed. Apparent recovery coefficients of spheres with a diameter smaller than 17 mm were significantly lower than those of spheres with a diameter of 17 mm and bigger (p < 0.001) for a tumor-to-background (T/B) ratio of 10:1 and a scan time of 10 min per bed position. With a T/B ratio of 10:1, the four largest spheres exhibit significantly higher RCs than those with a T/B ratio of 20:1 (p < 0.0001). For spheres with a diameter of 8 mm and less, alignment with the voxel grid potentially affects the RC. Evaluation of PET/CT scans using (semi-)quantitative measures such as SUVs should be performed with great caution, as SUVs are influenced by scanning and reconstruction parameters. Based on the evaluation of multiple reconstructions with different β of phantom scans, an intermediate β (600) is suggested as the optimal value for the reconstruction of clinical 68Ga-PSMA PET/CT scans, considering that both detectability and reproducibility are relevant.

Rijnsdorp|Sjoerd|S|
Roef|Mark J|MJ|
Arends|Albert J|AJ|

Bayesian penalized likelihood
68Ga-PSMA PET/CT
recovery coefficient
quantitative PET


Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers.

Abstract: Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals' use and provide preliminary information on drugs' ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs' bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure-activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k' (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure-retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood-brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k'(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models.

Ramirez|Daniela Andrea|DA|
Federici|María Fernanda|MF|
Altamirano|Jorgelina Cecilia|JC|
Camargo|Alejandra Beatriz|AB|
Luco|Juan María|JM|

permeability
biological barrier
organosulfur compounds
IAM
QSAR


Impact of Sexual Activity on the Risk of Male Genital Tumors: A Systematic Review of the Literature.

Abstract: Most cancers are related to lifestyle and environmental risk factors, including smoking, alcohol consumption, dietary habits, and environment (occupational exposures). A growing interest in the association between sexual activity (SA) and the development of different types of tumors in both men and women has been recorded in recent years. The aim of the present systematic review is to describe and critically discuss the current evidence regarding the association between SA and male genital cancers (prostatic, penile, and testicular), and to analyze the different theories and biological mechanisms reported in the literature. A comprehensive bibliographic search in the MEDLINE, Scopus, and Web of Science databases was performed in July 2021. Papers in the English language without chronological restrictions were selected. Retrospective and prospective primary clinical studies, in addition to previous systematic reviews and meta-analyses, were included. A total of 19 studies, including 953,704 patients were selected. Case reports, conference abstracts, and editorial comments were excluded. Men with more than 20 sexual partners in their lifetime, and those reporting more than 21 ejaculations per month, reported a decreased risk of overall and less aggressive prostate cancer (PCa). About 40% of penile cancers (PCs) were HPV-associated, with HPV 16 being the dominant genotype. Data regarding the risk of HPV in circumcised patients are conflicting, although circumcision appears to have a protective role against PC. Viral infections and epididymo-orchitis are among the main sex-related risk factors studied for testicular cancer (TC); however, data in the literature are limited. Testicular trauma can allow the identification of pre-existing TC. SA is closely associated with the development of PC through high-risk HPV transmission; in this context, phimosis appears to be a favoring factor. Sexual behaviors appear to play a significant role in PCa pathogenesis, probably through inflammatory mechanisms; however, protective sexual habits have also been described. A direct correlation between SA and TC has not yet been proven, although infections remain the most studied sex-related factor.

D005260:Female
D006801:Humans
D008297:Male
D011446:Prospective Studies
D012189:Retrospective Studies
D012307:Risk Factors
D012725:Sexual Behavior
D012747:Sexual Partners
D013736:Testicular Neoplasms

sexual activity
prostate cancer
penile cancer
testicular cancer
sex


Nationwide Trends in Acute and Chronic Pancreatitis Among Privately Insured Children and Non-Elderly Adults in the United States, 2007-2014.

Abstract:
BACKGROUND & AIMS
Epidemiologic analyses of acute pancreatitis (AP) and chronic pancreatitis (CP) provide insight into causes and strategies for prevention and affect allocation of resources to its study and treatment. We sought to determine current and accurate incidences of AP and CP, along with the prevalence of CP, in children and adults in the United States.

METHODS
We collected data from the Truven MarketScan Research Databases of commercial inpatient and outpatient insurance claims in the United States from 2007 through 2014 (patients 0-64 years old). We calculated the incidences of AP and CP and prevalence of CP based on International Classification of Diseases, 9th Revision diagnosis codes. Children were defined as 18 years or younger and adults as 19 to 64 years old.

RESULTS
The incidence of pediatric AP was stable from 2007 through 2014, remaining at 12.3/100,000 persons in 2014. Meanwhile, the incidence for adult AP decreased from 123.7/100,000 persons in 2007 to 111.2/100,000 persons in 2014. The incidence of CP decreased over time in children (2.2/100,000 persons in 2007 to 1.9/100,000 persons in 2014) and adults (31.7/100,000 persons in 2007 to 24.7/100,000 persons in 2014). The prevalences of pediatric and adult CP were 5.8/100,000 persons and 91.9/100,000 persons, respectively, in 2014. Incidences of AP and CP increased with age. We found little change in incidence during the first decade of life but linear increases starting in the second decade.

CONCLUSIONS
We performed a comprehensive epidemiologic analysis of privately insured, non-elderly adults and children with AP and CP in the United States. Changes in gallstone formation, smoking, and alcohol consumption, along with advances in pancreatitis management, may be responsible for the stabilization and even decrease in the incidences of AP and CP.

Sellers|Zachary M|ZM|
MacIsaac|Donna|D|
Yu|Helen|H|
Dehghan|Melody|M|
Zhang|Ke-You|KY|
Bensen|Rachel|R|
Wong|Jessie J|JJ|
Kin|Cindy|C|
Park|K T|KT|

Trends Epidemiology Inflammation Pancreas


In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis.

Abstract:
BACKGROUND
Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T-lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third-stage larva (L3) cultures and experimental infections in mice.

METHODS
The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 μM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1-aminododecan-2-yl) carbamate) and 18 (tert-butyl N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days.

RESULTS
In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9-39.1 μM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %).

CONCLUSIONS
These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis.

Legarda-Ceballos|Ana L|AL|
López-Abán|Julio|J|
Del Olmo|Esther|E|
Escarcena|Ricardo|R|
Bustos|Luis A|LA|
Rojas-Caraballo|Jose|J|
Vicente|Belén|B|
Fernández-Soto|Pedro|P|
San Feliciano|Arturo|A|
Muro|Antonio|A|

Strongyloidiasis Treatment Alkaneaminoalcohol Alkanediamine Anthelmintics


Annatto-Derived Tocotrienol Promotes Mineralization of MC3T3-E1 Cells by Enhancing BMP-2 Protein Expression via Inhibiting RhoA Activation and HMG-CoA Reductase Gene Expression.

Abstract:
Purpose
Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis and promote differentiation of pre-osteoblastic cells. However, the mechanism of action of AnTT in achieving these effects is unclear. This study aims to investigate the mechanism of action of AnTT on MC3T3-E1 pre-osteoblasts via the mevalonate pathway.

Methods
Murine pre-osteoblastic cells, MC3T3-E1, were cultured with the density of 1 × 104 cells/mL and treated with 4 concentrations of AnTT (0.001-1 µg/mL). Expression of HMG-CoA reductase (HMGR) gene was carried out using qPCR after treatment with AnTT for 21 days. RhoA activation and bone morphogenetic protein-2 (BMP-2) were measured using immunoassay after 9 and 15 days of AnTT treatment. Lovastatin was used as the positive control. Mineralized nodules were detected using Von Kossa staining after 21 days of AnTT treatment.

Results
The results showed that HMGR was up-regulated in the lovastatin group on day 9 and 21 compared to the control. Lovastatin also inhibited RhoA activation (day 9 and 15) and increased BMP-2 protein (day 15). On the other hand, AnTT at 0.001 μg/mL (day 3) and 0.1 μg/mL (day 21) significantly down-regulated HMGR gene expression compared to the control. On day 21, HMGR gene expression was significantly reduced in all groups compared to day 15. AnTT at 0.1 μg/mL significantly decreased RhoA activation on day 9 compared to the control. AnTT at 1 μg/mL significantly increased BMP-2 protein on day 15 compared to the control (P<0.05). Mineralized calcium nodules were more abundant in AnTT treated groups compared to the control on day 21.

Conclusion
AnTT suppresses the mevalonate pathway by downregulating HMGR gene expression and inhibiting RhoA activation, leading to increased BMP-2 protein in MC3T3-E1 cells. This explains the stimulating effects of AnTT on osteoblast mineralization.

tocotrienol
bone
osteoporosis
osteogenic
vitamin E


Small Bowel Neuroendocrine Tumors with Inguinal Metastases: A Diagnostic and Therapeutic Dilemma.

Abstract: Small bowel neuroendocrine tumors (NETs) are frequently characterized by a strong propensity to metastasize to the liver, mesentery, and peritoneum. However, only a few extra-abdominal metastatic sites have been reported in the published literature. The present paper implicates that primary small bowel NETs may unusually metastasize to the inguinal lymph nodes. Furthermore, we discuss the formidable diagnostic and therapeutic challenges associated with the metastatic NETs.

Inayat|Faisal|F|
Daly|Kevin P|KP|
Askarian|Farhad|F|
Saif|Muhammad W|MW|

small bowel
neuroendocrine tumors
inguinal lymph node
68ga-dotatate pet/ct
octreotide scintigraphy


Islet-like clusters derived from skeletal muscle-derived stem/progenitor cells for autologous transplantation to control type 1 diabetes in mice.

Abstract: A population of muscle-derived stem/progenitor cells (MDSPCs) contained in skeletal muscle is responsible for muscle regeneration. MDSPCs from mouse muscle have been shown to be capable of differentiating into pancreatic islet-like cells. However, the potency of MDSPCs to differentiate into functional islet-like cluster remains to be confirmed. The therapeutic potential of autologous MDSPCs transplantation on type 1 diabetes still remains unclear. Here, we investigated a four-stage method to induce the differentiation of MDSPCs into insulin-producing clusters in vitro, and tested the autologous transplantation to control type 1 diabetes in mice. MDSPCs isolated from the skeletal muscles of mice possessed the ability to form islet-like clusters through several stages of differentiation. The expressions of pancreatic progenitor-related genes, insulin, and islet-related genes were significantly upregulated in islet-like clusters determined by the quantitative reverse transcription polymerase chain reaction. The autologous islet-like clusters transplantation effectively improved hyperglycaemia and glucose intolerance and increased the survival rate in streptozotocin-induced diabetic mice without the use of immunosuppressants. Taken together, these results provide evidence that MDSPCs from murine muscle tissues are capable of differentiating into insulin-producing clusters, which possess insulin-producing ability in vitro and in vivo, and have the potential for autologous transplantation to control type 1 diabetes.

Lan|Kuo-Cheng|KC| Wang|Ching-Chia|CC| Yen|Yuan-Peng|YP| Yang|Rong-Sen|RS| Liu|Shing-Hwa|SH| Chan|Ding-Cheng|DC|

D016381:Islets of Langerhans Transplantation

islet-like clusters
autologous transplantation
differentiation
Diabetes mellitus
muscle-derived stem cells


Erratum on: The other-race and other-species effects in face perception-a subordinate-level analysis.

Abstract: [This corrects the article on p. 1068 in vol. 5, PMID: 25285092.].

other-species effect
configural processing
face perception
heterospecific faces
other-race effect
own-race advantage
own-species advantage
similarity


Neer Award 2012: cerebral oxygenation in the beach chair position: a prospective study on the effect of general anesthesia compared with regional anesthesia and sedation.

Abstract:
BACKGROUND
Devastating neurologic ischemic episodes, such as stroke and deafness, have occurred in patients undergoing shoulder surgery in the beach chair position. We hypothesized that awake patients would be able to avoid significant cerebral deoxygenation events (CDEs) compared with anesthetized patients when procedures were performed in the beach chair position.

MATERIALS AND METHODS
Sixty patients underwent elective shoulder surgery in the beach chair position. Thirty patients underwent an interscalene block and monitored sedation (awake group); 30 patients underwent general anesthesia (asleep group). Cerebral oxygenation saturation (Scto2) was measured during the procedure. Scto2 values below critical thresholds were defined as CDEs and treated.

RESULTS
Baseline mean arterial pressure and Scto2 values were lower in the asleep group during the operation (P < .0001). A higher incidence of CDEs was seen in the asleep group (56.7% vs 0% awake group), and more CDEs were seen per patient (2.97 in asleep vs 0 awake, P < .0001). Scto2 below a threshold value of 55% was seen in 23.3% in the asleep group vs 3.3% in the awake group. A total of 89 combined desaturation events were documented in the asleep vs 1 in the awake group (P < .0001).

CONCLUSIONS
Patients in the beach chair position treated with regional anesthesia and sedation had almost no cerebral desaturation events, unlike patients who had general anesthesia. Avoidance of general anesthesia in the beach chair position may reduce the risk of ischemic neurologic injury.

Koh|Jason L|JL|
Levin|Steven D|SD|
Chehab|Eric L|EL|
Murphy|Glenn S|GS|

oxygenation
beach chair
anesthesia
Shoulder surgery
Level II
Prospective Cohort Design
Treatment Study
cerebral perfusion


HN, N, Cα and Cβ assignments of the two periplasmic domains of Neisseria meningitidis DsbD.

Abstract: DsbD is a disulfide bond reductase present in the inner membrane of many Gamma-Proteobacteria. In the human pathogen Neisseria meningitidis, DsbD is required for viability and represents a potential target for the development of antibiotics. Here we report the chemical shift assignments (HN, N, Cα and Cβ) for the reduced and oxidized forms of the two periplasmic domains of N. meningitidis DsbD, n-NmDsbD and c-NmDsbD. The backbone amide resonances in all four forms were completely assigned, and the secondary structures for the core regions of the proteins were calculated using 13Cαβ shifts. The reduced and oxidized forms of each domain have similar secondary shifts suggesting they retain the same fold. We anticipate that these data will provide an important basis for studying the interaction between n-NmDsbD and c-NmDsbD, which is required for electron transfer across the bacterial cytoplasmic membrane.

D019906:Nuclear Magnetic Resonance, Biomolecular

Neisseria meningitidis
DsbD
Bacterial reductase
Disulfide reduction


Elevated Systemic Inflammatory Burden and Cardiovascular Risk in Young Adults with Endodontic Apical Lesions.

Abstract:
INTRODUCTION
The aim of this study was to assess whether apical lesions are associated with inflammatory serum markers of cardiovascular risk, especially high-sensitivity C-reactive protein (hsCRP), in young adults.

METHODS
In this cross-sectional study, otherwise healthy individuals with apical lesions of endodontic origin (ALEOs) and a clinical diagnosis of asymptomatic apical periodontitis and controls aged between 18 and 40 years were included. Patients' sociodemographic characteristics, medical history, and classic cardiovascular risk factors were recorded, and the pathobiological determinants of atherosclerosis in youth score was calculated. Oral clinical and radiographic examinations were performed. Blood samples were collected to determine the lipid profile, glycated hemoglobin, hsCRP, immunoglobulin G, interleukin (IL)-6, IL-10, IL-12p70, matrix metalloproteinase 8, soluble vascular cellular adhesion molecule-1, soluble intercellular adhesion molecule-1, and soluble E-selectin. Bivariate and multivariate analyses adjusting for oral and classic cardiovascular risk factors were performed.

RESULTS
hsCRP levels were significantly higher in ALEO patients versus controls (median = 2.54 vs 0.78), whereas the pathobiological determinants of atherosclerosis in youth score was comparable among the groups. Also, the levels of IL-6, matrix metalloproteinase 8, and soluble E-selectin were significantly higher in ALEO patients. hsCRP, IL-6, and IL-12 correlated with soluble adhesion molecules. Bivariate analysis based on hsCRP serum concentrations ≥1 mg/L showed an odds ratio (OR) = 6.8, and the risk increased 3.3 times for an additional ALEO. In multivariate analysis, ALEO was significantly associated with hsCRP levels ≥1 mg/L (OR = 5.1-12.8) independently of the adjustment model. ALEO also associated with CRP levels >3 mg/L, which was significant after the adjustment for covariates (OR = 4.0).

CONCLUSIONS
ALEO is associated with the systemic inflammatory burden and cardiovascular risk determined by hsCRP, supporting a mechanistic link for cardiovascular diseases in young adults.

Garrido|Mauricio|M|
Cárdenas|Angélica M|AM|
Astorga|Jessica|J|
Quinlan|Francisca|F|
Valdés|Macarena|M|
Chaparro|Alejandra|A|
Carvajal|Paola|P|
Pussinen|Pirkko|P|
Huamán-Chipana|Patricia|P|
Jalil|Jorge E|JE|
Hernández|Marcela|M|

D018746:Systemic Inflammatory Response Syndrome

C-reactive protein
E-selectin
Cardiovascular diseases
interleukin 6
periapical periodontitis


Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma.

Abstract:
BACKGROUND
Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown.

OBJECTIVE
To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism.

METHODS
The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α, and TGF-β1, and serum from patients with asthma were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analysed.

RESULTS
Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodelling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α, and TGF-β1, and serum from patients with asthma increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein, which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis, and cell proliferation of ASMCs and attenuated airway smooth muscle remodelling in mouse asthma models.

CONCLUSIONS AND CLINICAL RELEVANCE
Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway smooth muscle remodelling in asthma.

Rao|S-S|SS|
Mu|Q|Q|
Zeng|Y|Y|
Cai|P-C|PC|
Liu|F|F|
Yang|J|J|
Xia|Y|Y|
Zhang|Q|Q|
Song|L-J|LJ|
Zhou|L-L|LL|
Li|F-Z|FZ|
Lin|Y-X|YX|
Fang|J|J|
Greer|P A|PA|
Shi|H-Z|HZ|
Ma|W-L|WL|
Su|Y|Y|
Ye|H|H|

D000076225:Mechanistic Target of Rapamycin Complex 2

D000076226:Rapamycin-Insensitive Companion of mTOR Protein

remodelling
asthma
calpain
airway smooth muscle cells
PI3K/Akt pathway


Survey of high-risk pool enrollees suggests that targeted transition education and outreach should begin soon.

Abstract: Several provisions of the Affordable Care Act make state and federal high-risk pools unnecessary beginning in January 2014. As a result, thousands of enrollees in those pools will be transferred to Medicaid and the new state and federal insurance exchanges. Our study analyzed new survey data collected from enrollees in the country's oldest and largest state-based high-risk pool, the Minnesota Comprehensive Health Association. We estimate that approximately half of the enrollees in that pool will qualify for Medicaid or premium subsidies in the exchange. More than 60 percent of the enrollees reported being somewhat or very unfamiliar with health care reform and the resulting changes to their current coverage. Their concerns about the expected impact of health reform varied by income, geography, and level of deductible. Targeting education and outreach information to address these concerns will be critical for this population's smooth transition to new coverage.

Blewett|Lynn A|LA|
Lukanen|Elizabeth|E|
Call|Kathleen T|KT|
Dahlen|Heather|H|

D007722:Health Knowledge, Attitudes, Practice

D058991:Patient Protection and Affordable Care Act

Insurance
Health Reform
Insurance Coverage
Public Health
Safety-Net Systems


Antibacterial Nanopillar Array for an Implantable Intraocular Lens.

Abstract: Postsurgical intraocular lens (IOL) infection caused by pathogenic bacteria can result in blindness and often requires a secondary operation to replace the contaminated lens. The incorporation of an antibacterial property onto the IOL surface can prevent bacterial infection and postoperative endophthalmitis. This study describes a polymeric nanopillar array (NPA) integrated onto an IOL, which captures and eradicates the bacteria by rupturing the bacterial membrane. This is accomplished by changing the behavior of the elastic nanopillars using bending, restoration, and antibacterial surface modification. The combination of the polymer coating and NPA dimensions can decrease the adhesivity of corneal endothelial cells and posterior capsule opacification without causing cytotoxicity. An ionic antibacterial polymer layer is introduced onto an NPA using an initiated chemical vapor deposition process. This improves bacterial membrane rupture efficiency by increasing the interactions between the bacteria and nanopillars and damages the bacterial membrane using quaternary ammonium compounds. The newly developed ionic polymer-coated NPA exceeds 99% antibacterial efficiency against Staphylococcus aureus, which is achieved through topological and physicochemical surface modification. Thus, this paper provides a novel, efficient strategy to prevent postoperative complications related to bacteria contamination of IOL after cataract surgery.

Choi|Goro|G|
Song|Younseong|Y|
Lim|Hyungjun|H|
Lee|Song Ha|SH|
Lee|Hyung Keun|HK|
Lee|Eunjung|E|
Choi|Bong Gill|BG|
Lee|Jae Jong|JJ|
Im|Sung Gap|SG|
Lee|Kyoung G|KG|0000-0003-2691-0910

D000900:Anti-Bacterial Agents
D042783:Endothelial Cells
D007908:Lens, Crystalline
D007910:Lenses, Intraocular
D011108:Polymers

antibacterial nanopillars
surface modification
initiated chemical vapor deposition
intraocular lenses
polymer nanopillar arrays


Identifying functional modules for coronary artery disease by a prior knowledge-based approach.

Abstract: Until recently, the underlying genetic mechanisms for coronary artery disease (CAD) have been largely unknown, with just a list of genes identified accounting for very little of the disease in the population. Hence, a systematic dissection of the sophisticated interplays between these individual disease genes and their functional involvements becomes essential. Here, we presented a novel knowledge-based approach to identify the functional modules for CAD. First, we selected 266 disease genes in CADgene database as the initial seed genes, and used PPI knowledge as a guide to expand these genes into a CAD-specific gene network. Then, we used Newman's algorithm to decompose the primary network into 14 compact modules with high modularity. By analysis of these modules, we further identified 114 hub genes, all either directly or indirectly associated with CAD. Finally, by functional analysis of these modules, we revealed several novel pathogenic mechanisms for CAD (for examples, some yet rarely concerned like peptide YY receptor activity, Fc gamma R-mediated phagocytosis and actin cytoskeleton regulation etc.).

Li|Haoli|H| Zuo|Xiaoyu|X| Ouyang|Ping|P| Lin|Meihua|M| Zhao|Zhong|Z| Liang|Yan|Y| Zhong|Shouqiang|S| Rao|Shaoqi|S|

D020022:Genetic Predisposition to Disease

Coronary artery disease
CAD
PPI
Data mining
GO
Gene Ontology
Gene annotation
Gene module
HPRD
Human Protein Reference Database
Protein interaction maps
Protein–protein interaction
VSMC
Vascular smooth muscle cell


Overall care cost comparison between robotic and laparoscopic surgery for endometrial and cervical cancer.

Abstract:
OBJECTIVE
The aim of our medico-economic study was to compare robotic surgery cost with conventional laparoscopic cost in endometrial and cervical cancer.

STUDY DESIGN
Our study included laparoscopic and robot-assisted procedures (radical hysterectomies and lymphadenectomies) for endometrial or cervical cancer ever since first using the Da Vinci® in 2008 within a hospital setting. In the hospital perspective, direct costs were determined by examining the overall medical pathway for each type of intervention. Actual costs were calculated for 27 conventional laparoscopic procedures and for 30 robot-assisted procedures including initial cost of the robot and its maintenance. We estimated the complete medical "overall care" costs by adding the costs of consultations, surgery and post-operative hospital stay to the costs of any eventual emergency consultation and/or hospitalisation within the two months that followed surgery. A sensitivity analysis was performed to evaluate the effects of variable modulations.

RESULTS
For endometrial cancer, surgical procedure cost for robotic-assisted surgery was €7402 compared to €2733 for conventional laparoscopic surgery. When considering overall medical care, the patient treatment average cost was €6666 for the laparoscopic group (with an average length of stay of 5.27 days) as compared to €10,816 for robotic group (with an average hospital stay of 4.60 days), p=0.39. For cervical cancer, average surgical cost with robotic-assisted surgery was €8501 compared to conventional laparoscopic surgery at €3239. For cervical cancer, overall care average cost was €7803 for the laparoscopic group (with an average length of stay of 5.83 days) as compared to €12,211 for the robotic group (with an average hospital stay of 4.70 days) p=0.07. Sensitivity analysis results confirmed the cost overrun with the use of robotic assisted surgery.

CONCLUSIONS
Conventional laparoscopy was less expensive in our institution than robotic-assisted surgery for the surgery of endometrial (1:2.7) and cervical (1:2.6) cancers. When considering overall medical care, the use of robotic-assisted surgery was found to be 1.6 times more expensive than conventional surgery.

Desille-Gbaguidi|H|H| Hebert|T|T| Paternotte-Villemagne|J|J| Gaborit|C|C| Rush|E|E| Body|G|G|

Robotic assistance
Cost analysis
Laparoscopic hysterectomy
Robotic hysterectomy
Robotic versus laparoscopic


Comparison of health-related quality of life (HRQoL) among healthy, obese and chronically ill Iranian children.

Abstract:
BACKGROUND
Health-related quality of life (HRQoL) has frequently been compared between both healthy and obese children and healthy and chronically ill children; however, there is glaring lack of evidence regarding comparison of HRQoL in obese children with their counterparts with chronic diseases. Therefore, this study aimed to compare HRQoL among healthy, obese and chronically ill children.

METHODS
This cross sectional study was conducted among 802 children (8-12 years) who were recruited via convenience sampling method. Participants were 98 healthy, 102 obese and 602 chronically ill children with six groups of chronic conditions including different types of cancer, rheumatoid arthritis, chronic gastrointestinal, kidney, neurologic and respiratory diseases. HRQoL was assessed using the Iranian version of the PedsQL questionnaire and both reports including child self-report and parent proxy-report were obtained. To compare subscales and total scores of HRQoL among healthy, obese and six groups of chronically ill children, the general linear model was used.

RESULTS
Mean self-reported HRQoL total scores were 73.7 ± 13.3 and 74.6 ± 11.8 in girls and boys respectively; based on the parents' reports, mean HRQoL total scores were 71.6 ± 15.4 and 71.4 ± 13.0 in girls and boys respectively. From the prespectives of both children and parents, HRQoL total score was significantly lower in obese girls compared to both healthy girls and girls with chronic gastrointestinal, kidney, neurologic and respiratory diseases. Considering both children's and parents' reports, HRQoL total score was significantly lower in obese boys compared to both healthy boys and boys with chronic respiratory diseases. In terms of subscales of HRQoL, the impairment of HRQoL in obese children, compared to their counterparts with other chronic diseases, was more common in social functioning and physical functioning subscales, specifically in girls.

CONCLUSION
Obese children reported poorer HRQoL compared to their healthy counterparts, as well as their counterparts with chronic diseases. Current findings emphasize the important impact of childhood obesity on the perceived health of these children, particularly in the social dimension, underscoring thereby the designing, planning and implementation of health promotion programs for prevention and treatment of childhood obesity.

Jalali-Farahani|Sara|S|
Shojaei|Fahimeh Alsadat|FA|
Parvin|Parnian|P|
Amiri|Parisa|P|

Obesity
Children
Chronic diseases
Health related quality of life
Iran


Acupuncture for the Treatment of Pain - A Mega-Placebo?

Abstract: Several control conditions, such as penetrating sham acupuncture and non-penetrating placebo needles, have been used in clinical trials on acupuncture effects in chronic pain syndromes. All these control conditions are surprisingly effective with regard to their analgesic properties. These findings have fostered a discussion as to whether acupuncture is merely a placebo. Meta-analyses on the clinical effectiveness of placebo revealed that placebo interventions in general have minor, clinically important effects. Only in trials on pain and nausea, including acupuncture studies, did placebo effects vary from negligible to clinically important. At the same time, individual patient meta-analyses confirm that acupuncture is effective for the treatment of chronic pain, including small but statistically significant differences between acupuncture and sham acupuncture. All acupuncture control conditions induce de qi, a distinct stimulation associated with pain and needling which has been shown to be a nociceptive/pain stimulus. Acupuncture therefore probably activates the pain matrix in the brain in a bottom-up fashion via the spino-thalamic tract. Central nervous system effects of acupuncture can be modulated through expectations, which are believed to be a central component of the placebo response. However, further investigation is required to determine how strong the influence of placebo on the attenuation of activity in the pain matrix really is. A meta-analysis of individual participant functional magnetic imaging data reveals only weak effects of placebo on the activity of the pain network. The clinical acupuncture setting is comprised of a combination of a distinct neurophysiological stimulus, the needling stimulus/experience, and a complex treatment situation. A broader definition of placebo, such as that proposed by Howick (2017) acknowledges a role for expectation, treatment context, emotions, learning, and other contextual variables of a treatment situation. The inclusion of particular treatment feature as a definitional element permits a contextual definition of placebo, which in turn can be helpful in constructing future clinical trials on acupuncture.

acupuncture
pain
sham acupuncture
placebo
placebo needles
pain matrix
expectation


Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers: Real-Life Observation of Consecutive Patients.

Abstract:
BACKGROUND
Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear.

METHODS
We analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing to assess EC. Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%.

RESULTS
Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), 64% with heart failure, chronotropic incompetence was present in 80.7%. EC assessed as peak oxygen uptake was lower in the group with chronotropic incompetence, 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = -0.17, p < 0.001) and presence of heart failure (β = -3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI accounted for more than one-third of the variance in EC explained by the model (adjusted R2 = 59.8%).

CONCLUSIONS
In patients taking beta-blockers, presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

chronotropic incompetence
exercise capacity
exercise test
chronotropic index
oxygen uptake
adrenergic beta antagonists


The Diagnostic-Therapeutic Care Pathway in Psoriasis: Towards ISO 9001:2015 Certification.

Abstract: Background and objectives: Psoriasis (Pso) is a common skin condition characterized by a strong psychosocial impact, and is nowadays accepted as a systemic immune-mediated inflammatory disease. Diagnostic-Therapeutic Care Pathways (DTCPs) represent a predefined sequence of diagnostic, therapeutic, and assistance activities that integrate the participation of several specialists to obtain, for each patient, the correct diagnosis and thus the most appropriate therapy. A DTCP was validated in our dermatology clinic (AOU Maggiore della Carità, Novara, Italy). The validation process included the detailed elaboration of a protocol of diagnosis, staging of care, therapies, and follow-up of the patient with Pso. The formalization and adaptation of our DTCP resulted in ISO 9001: 2015 certification in May 2019. Materials and methods: This process involved several stages, including analysis of context and the identification of (i) targets, (ii) indicators, and (iii) service providers. The evaluation was based on a cohort of over 200 patients affected by moderate to severe Pso, who were treated and followed-up at our institution from September 2017 to April 2019. Results: The ISO 9001:2015 quality certification process allowed us to identify our weaknesses, i.e., the long waiting times for the first visit and the reduced physician-patient ratio, but also our strengths, such as the commitment to clinical research, effective collaboration with other specialists, the efficient use of technological and human resources, and attention to ensuring patient follow-up. Conclusions: In qualifying for and achieving the ISO Quality Management System (QMS) certification we were heartened to realize that our basic methodology and approach were fit for purpose. The implementation of the ISO QMS helped us to reorganize our priorities by placing the patient at the center of the process and raising awareness that Pso is not just a skin disease.

Veronese|Federica|F|0000-0001-6438-5171 Graziola|Francesca|F| Cammarata|Edoardo|E| Andreassi|Marco|M| Mazzoletti|Vanessa|V| Taglietti|Camilla|C| Navarra|Gaia|G| Savoia|Paola|P|0000-0002-1636-8411 Tiberio|Rossana|R|

psoriasis
ISO 9001:2015 certification
quality management system
diagnostic–therapeutic care pathway
quality improvement


Flexible Bonding of the Phosph(V)azane Dianions [S(E)P(μ-NtBu)]22.

Abstract: Oxidation of the PIII dianion [S-P(μ-NtBu)]22- (1) with elemental sulphur, selenium and tellurium gives the PV dianions [(S)(E)P(μ-NtBu)]22- (E = S (6 a), Se (6 b), Te (6 c)). Although 6 c proves to be too unstable, the S,S-dianion 6 a and ambidentate S,Se-dianion 6 b are readily transferred intact to main group and transition metal elements, producing a range of new cage and coordination compounds. While their coordination characteristics are in many ways similar to closely-related isoelectronic phosph(V)azane anions [(E)(RN=)P(μ-NtBu)]22- , the sterically unhindered nature of 6 introduces an expanded range of coordination modes, that is, facial S,S- and Se,Se-bonding as well as side-on S,Se-coordination. All of these bonding modes are observed for the amibidentate S,Se dianion 6 b.

ambidentate
transition metal
ligands
phosph(III/V)azanes
phosphorus


CDCP1-targeted nanoparticles encapsulating phase-shift perfluorohexan for molecular US imaging in vitro.

Abstract:
BACKGROUND
Molecular targeted contrast-enhanced ultrasound (CEUS) imaging is a potential imaging strategy to improve the diagnostic accuracy of conventional ultrasound (US) imaging. US contrast agents are usually micrometer-sized and non-target gas bubbles while nano-sized and targeted agents containing phase-shift materials absorb more attractions for their size and the liquid core and excellent molecular imaging effect.

METHODS
PLGA12k-mPEG2k-NH2, DSPE-mPEG2k and perfluorohexan (PFH) were used to construct a new targeted ultrasound contrast agent with CUB domain-containing protein 1 (CDCP1) receptor for the detection and diagnosis of prostate cancer. The potential of tumor-targeted nanoparticles (CDCP1-targeted perfluorohexan-loaded phase-transitional nanoparticles, anti-CDCP1 NPs) as contrast agents for ultrasound (US) imaging was assessed in vitro. Moreover, studies on the cytotoxicity and the targeting ability of anti-CDCP1 NPs assisted by US were carried out.

RESULTS
The results showed that anti-CDCP1 NPs had low cytotoxicity, and with the increasing of polymer concentration in anti-CDCP1 NPs, the CEUS imaging of agent gradually enhanced, and enhanced imaging associated with the length of observing time. Furthermore, it was testified that anti-CDCP1 assisted the agent to target cells expressing CDCP1, which demonstrated the active targeting of anti-CDCP1 NPs in vitro.

CONCLUSION
All in all, the feasibility of using targeted anti-CDCP1 NPs to enhance ultrasound imaging has been demonstrated in vitro, which laid a solid foundation for molecular US imaging in vivo, and anti-CDCP1 NPs might have a great clinical application prospect.

Zhao|Meng|M| Zhu|Yunkai|Y| Zhang|Yanhua|Y| Yang|Xupeng|X| Duan|Yourong|Y| Chen|Yaqing|Y| Sun|Ying|Y|

contrast agent
prostate cancer
Targeted nanoparticle


Unfolding biological properties of a versatile dicopper(II) precursor and its two mononuclear copper(II) derivatives.

Abstract: Synthesis, inter-conversions and biological study of the dichloro bridged dicopper(II) compound [CuLCl]2 (1) and its two mononuclear derivatives [CuLCl(H2O)]·H2O (2) and [CuLCl(py)] (3) (HL=2-(2-pyridylmethyleneamino)benzenesulfonic acid) are described. The dimeric compound 1 collapses into monomers 2 and 3 in the presence of coordinating solvents, water and pyridine, respectively, and 1 is regenerated upon simple stirring of 2 or 3 in methanol. The reactions of 1 with neutral (present study) and charged (earlier studies) ligands result in monomeric and multimeric compounds, respectively, attesting that it is a versatile dicopper(II) precursor. The anticancer activity of these copper complexes (1-3) was screened against lung (A-549) and breast (MDA-MB-231) human cancer cell lines. The IC50 (half maximal inhibitory concentration) value for one (3) of the compounds suggests preferential cytotoxicity against breast cancer MDA-MB-231 cell line. Furthermore, the IC50 value obtained for complex 3 is found to be almost two-fold times cytotoxic than the standard drug cisplatin. In addition, the underlying possible mechanism of its apoptosis-inducing efficacy in MDA-MB-231 cells has been rationalized by using flow cytometry (FACS) and Hoechst 33342/propidium iodide (PI) fluorescence staining. The stimulation of apoptotic induction for complex 3 has further been affirmed by reactive oxygen species (ROS) generation and mitochondrial aggregations studies.

Paul|Anup|A|
Hazra|Susanta|S|
Sharma|Gunjan|G|
Guedes da Silva|M Fátima C|MFC|
Koch|Biplob|B|
Pombeiro|Armando J L|AJL|

Reactive oxygen species
Cytotoxicity in vitro
Fluorescence activated cell sorting
Mitochondrial distribution
Sulfonated Schiff base copper(II)


The Krebs Cycle Connection: Reciprocal Influence Between Alternative Splicing Programs and Cell Metabolism.

Abstract: Alternative splicing is a pervasive mechanism that molds the transcriptome to meet cell and organism needs. However, how this layer of gene expression regulation is coordinated with other aspects of the cell metabolism is still largely undefined. Glucose is the main energy and carbon source of the cell. Not surprisingly, its metabolism is finely tuned to satisfy growth requirements and in response to nutrient availability. A number of studies have begun to unveil the connections between glucose metabolism and splicing programs. Alternative splicing modulates the ratio between M1 and M2 isoforms of pyruvate kinase in this way determining the choice between aerobic glycolysis and complete glucose oxidation in the Krebs cycle. Reciprocally, intermediates in the Krebs cycle may impact splicing programs at different levels by modulating the activity of 2-oxoglutarate-dependent oxidases. In this review we discuss the molecular mechanisms that coordinate alternative splicing programs with glucose metabolism, two aspects with profound implications in human diseases.


In-Line Detection with Microfluidic Bulk Acoustic Wave Resonator Gas Sensor for Gas Chromatography.

Abstract: A microfluidic film bulk acoustic wave resonator gas sensor (mFBAR) adapted specifically as an in-line detector in gas chromatography was described. This miniaturized vapor sensor was a non-destructive detector with very low dead volume (0.02 μL). It was prepared by enclosing the resonator in a microfluidic channel on a chip with dimensions of only 15 mm × 15 mm × 1 mm. The device with polymer coating showed satisfactory performance in the detection of organophosphorus compound, demonstrating a very low detection limit (a dozen parts per billion) with relatively short response time (about fifteen seconds) toward the simulant of chemical warfare agent, dimethyl methylphosphonate. The in-line detection of the mFBAR sensor with FID was constructed and employed to directly measure the concentration profile on the solid surface by the mFBAR with the controlled concentration profile in the mobile phase at the same time. The difference of peak-maximum position between mobile phase and solid phase could be a convenient indicator to measure mass transfer rate. With the response of the mFBAR and FID obtained in one injection, an injection mass-independent parameter can be calculated and used to identify the analyte of interest.

Hu|Jizhou|J| Qu|Hemi|H| Pang|Wei|W| Duan|Xuexin|X|0000-0002-7550-3951

in-line detection
bulk acoustic wave resonator
microfluidic channel
multi-dimensional gas chromatography


The Interfacial Interactions of Glycine and Short Glycine Peptides in Model Membrane Systems.

Abstract: The interactions of amino acids and peptides at model membrane interfaces have considerable implications for biological functions, with the ability to act as chemical messengers, hormones, neurotransmitters, and even as antibiotics and anticancer agents. In this study, glycine and the short glycine peptides diglycine, triglycine, and tetraglycine are studied with regards to their interactions at the model membrane interface of Aerosol-OT (AOT) reverse micelles via 1H NMR spectroscopy, dynamic light scattering (DLS), and Langmuir trough measurements. It was found that with the exception of monomeric glycine, the peptides prefer to associate between the interface and bulk water pool of the reverse micelle. Monomeric glycine, however, resides with the N-terminus in the ordered interstitial water (stern layer) and the C-terminus located in the bulk water pool of the reverse micelle.

glycine
reverse micelles
1H NMR
AMPs
pKa


Burden and Transmission Risks of Viral Hepatitis in Southern Ethiopia: Evidence Needed for Prevention and Control Measures.

Abstract:
Background
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are significant causes of liver-associated morbidity and mortality for millions of people globally. Ethiopia is one of the viral hepatitis-endemic countries with no national strategy for surveillance and limited data. As such, this study aimed to investigated the extent and associated risk factors of HBV and HCV among community members in southern Ethiopia.

Methods
A community-based cross-sectional study was conducted from January 2020 to August 2020. A structured questionnaire was used to collect behavioral and sociodemographic data. Serum samples were collected and assayed for seromarkers of HBV (HBsAg, anti-HBc, and anti-HBs) and HCV (anti-HCV) using ELISAs. In HBsAg-positive samples, HBV DNA was further quantified using RT-PCR. Data were entered into EpiData 3.1 and analyzed using SPSS 21.0. Descriptive statistics and logistic regression analysis were employed.

Results
The study included 693 participants. Seromarkers for HBsAg, anti-HCV, anti-HBc, and anti-HBs were found to be 9.5%, 1.4%, 31.1%, and 14.3%, respectively. In 66 HBsAg positives, 57 (86.4%) had quantifiable HBV DNA. Prevalence of current HBV infection (HBsAg+, anti-HBc+, anti-HBs-) and lifetime exposure (positive for either HBsAg or anti-HBc) to HBV were 8.7% and 31.9%, respectively, and 63.1% of participants were vulnerable or had no evidence of prior HBV infection (HBsAg-, anti-HBc-, anti-HBs-). On multivariate logistic regression analysis, multiple sexual contacts, family history of hepatitis infection, alcohol consumption, and khat chewing were significantly associated with HBV. The seroprevalence of HBV was relatively high in this study area.

Conclusion
This study showed high prevalence of HBV infection, but low prevalence of HCV. This indicates that HBV is a major health problem in this community. Population-based surveillance, care, and treatment, as well as behavioral change and education programs, should be enhanced to minimize risk exposure.

Beykaso|Gizachew|G| Mulu|Andargachew|A| Giday|Mirutse|M| Berhe|Nega|N|0000-0001-6959-989X Selamu|Markos|M|0000-0002-3983-2440 Mihret|Adane|A| Teklehaymanot|Tilahun|T|

southern Ethiopia
HBV
HCV
community-based
seroprevalence


Acute disseminated encephalomyelitis in a COVID-19 pediatric patient.

Abstract: The authors present a case of acute disseminated encephalomyelitis in a COVID-19 pediatric patient with positive SARS-CoV2 markers from a nasopharyngeal swab. A previously healthy 12-year-old-girl presented with a skin rash, headache, and fever. Five days after that, she had an acute, progressive, bilateral, and symmetrical motor weakness. She evolved to respiratory failure. Magnetic resonance imaging (MRI) of the brain and cervical spine showed extensive bilateral and symmetric restricted diffusion involving the subcortical and deep white matter, a focal hyperintense T2/FLAIR lesion in the splenium of the corpus callosum with restricted diffusion, and extensive cervical myelopathy involving both white and gray matter. Follow-up examinations of the brain and spine were performed 30 days after the first MRI examination. The images of the brain demonstrated mild dilatation of the lateral ventricles and widespread widening of the cerebral sulci, complete resolution of the extensive white matter restricted diffusion, and complete resolution of the restricted diffusion in the lesion of the splenium of the corpus callosum, leaving behind a small gliotic focus. The follow-up examination of the spine demonstrated nearly complete resolution of the extensive signal changes in the spinal cord, leaving behind scattered signal changes in keeping with gliosis. She evolved with partial clinical and neurological improvement and was subsequently discharged.

de Miranda Henriques-Souza|Adélia Maria|AM|https://orcid.org/0000-0002-5303-5528

de Melo|Ana Cláudia Marques Gouveia|ACMG|https://orcid.org/0000-0003-1909-568X

de Aguiar Coelho Silva Madeiro|Bianca|B|https://orcid.org/0000-0002-0138-8209

COVID-19
ADEM
Brain diseases
Central Nervous System
Child
Spinal cord diseases