Low radiographic muscle density is associated with lower overall and disease-free survival in early-stage colorectal cancer patients.

Abstract:
BACKGROUND
In cancer patients with a poor prognosis, low skeletal muscle radiographic density is associated with higher mortality. Whether this association also holds for early-stage cancer is not very clear. We aimed to study the association between skeletal muscle density and overall mortality among early-stage (stage I-III) colorectal cancer (CRC) patients. Furthermore, we investigated the association between skeletal muscle density and both CRC-specific mortality and disease-free survival in a subset of the study population.

METHODS
Skeletal muscle density was assessed in 1681 early-stage CRC patients, diagnosed between 2006 and 2015, using pre-operative computed tomography images. Adjusted Cox proportional hazard models were used to evaluate the association between muscle density and overall mortality, CRC-specific mortality and disease-free survival.

RESULTS
The median follow-up time was 48 months (range 0-119 months). Low muscle density was detected in 39% of CRC patients. Low muscle density was significantly associated with higher mortality (low vs. normal: adjusted HR 1.91, 95% CI 1.53-2.38). After stratification for comorbidities, the association was highest in patients with ≥ 2 comorbidities (HR 2.11, 95% CI 1.55-2.87). Furthermore, low skeletal muscle density was significantly associated with poorer disease-free survival (HR 1.68, 95% CI 1.14-2.47), but not with CRC-specific mortality (HR 1.68, 95% CI 0.89-3.17) in a subset of the study population.

CONCLUSION
In early-stage CRC patients, low muscle density was significantly associated with higher overall mortality, and worse disease-free survival.

D000368:Aged
D000369:Aged, 80 and over
D003110:Colonic Neoplasms
D015179:Colorectal Neoplasms
D018572:Disease-Free Survival
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D018482:Muscle, Skeletal
D009367:Neoplasm Staging
D011379:Prognosis
D016016:Proportional Hazards Models
D011446:Prospective Studies
D015996:Survival Rate
D014057:Tomography, X-Ray Computed

Survival
Colorectal cancer
Mortality
Skeletal muscle density


Change-of-Direction Ability of Para-Footballers With Cerebral Palsy Under a New Evidence-Based and Sport-Specific Classification System.

Abstract:
PURPOSE
This study aimed (1) to explore the validity and reliability of a new and specific change-of-direction (COD) test that requires dribbling skills to classify international footballers with cerebral palsy (CP) and compare it with another valid and reliable COD test without ball dribbling and (2) to probe whether both tests can discriminate between the new CP football classes (ie, FT1, FT2, and FT3) established worldwide in 2018.

METHODS
This study involved 180 international para-footballers with CP from 23 national teams at the 3 regional competitions held in 2018. They performed 2 COD tests, the modified agility test (no dribbling skills) and the dribbling speed test (DST).

RESULTS
Reliability was excellent for both the modified agility test (intraclass correlation coefficient [ICC]2,1 = .91, SEM = 5.75%) and the DST (ICC2,1 = .92, SEM = 4.66%). The modified agility test and DST results were highly to very highly correlated to one another for the whole group and considering the sport classes (r = .60-.80; P < .001). A 1-way analysis of variance showed significant differences between sport classes in both tests (P < .001). However, among classes, there were significant differences between FT1 and FT2 and FT3 (P < .01, effect size = large) and low to moderate effect sizes between FT2 and FT3 for either test.

CONCLUSION
The DST appears to be valid and reliable to classify CP football players within the new classification system. Regression analysis revealed that 18.2% of the variance in the new sport classes could be explained by the 2 examined tests.

Peña-González|Iván|I| Roldan|Alba|A| Toledo|Carlos|C| Urbán|Tomás|T| Reina|Raúl|R|

D064846:Sports for Persons with Disabilities

dribbling
agility
brain impairment
paralympics
soccer


Evaluation of the dose metric for acute lung inflammogenicity of fast-dissolving metal oxide nanoparticles.

Abstract: Although surface area metric was suggested as an appropriate dose metric for acute lung inflammation of NPs, it might not be effective for fast-dissolving NPs because they lose their reactive surface when dissolved in the phagolysosomes. Herein, we evaluated the dose metric for fast-dissolving NPs using a rat intratracheal instillation model. A panel of fast-dissolving NPs (CoO, CuO and ZnO) and their constituent metal ions (CoCl2, CuCl2 and ZnCl2) were compiled and each compound was intratracheally instilled into the lungs of female Wistar rats at the same molar concentrations in the NP doses (40, 100 and 400 μg/rat). The toxicity endpoints including cytological and biochemical data in bronchoalveolar lavage fluid were evaluated at 24 h after instillation. To evaluate the dose metric, each toxicity endpoint was plotted against the instilled dose (mass or surface area) or the equivalent dose (mass or surface area) that was weighted by the ratio of specific dose-generated responses between metal chlorides. Dose-response curves of fast-dissolving NPs about percentage of granulocytes, lactate dehydrogenase levels and total protein levels showed similar pattern but slightly less potential than those of their respective metal chlorides. When each toxicity endpoint was plotted against the equivalent mass dose, three types of NPs showed more overlapping dose-response curves than other dose metrics. In conclusion, this study implies that the equivalent mass dose is an appropriate dose metric for fast-dissolving NPs and the main factor determining the slope of the dose-response curve is the intrinsic toxicity of the their constituent ions.

Jeong|Jiyoung|J|
Lee|Seonghan|S|
Kim|Sung-Hyun|SH|
Han|Youngju|Y|
Lee|Dong-Keon|DK|
Yang|Jun-Young|JY|
Jeong|Jayoung|J|
Roh|Changhyun|C|
Huh|Yun Suk|YS|
Cho|Wan-Seob|WS|

metal oxide
intratracheal instillation
equivalent dose
Dose-metric
fast-dissolving nanoparticles


Health Disparities Research with American Indian Communities: The Importance of Trust and Transparency.

Abstract: American Indian and Alaska Native (AI/AN) communities experience notable health disparities associated with substance use, including disproportionate rates of accidents/injuries, diabetes, liver disease, suicide, and substance use disorders. Effective treatments for substance use are needed to improve health equity for AI/AN communities. However, an unfortunate history of unethical and stigmatizing research has engendered distrust and reluctance to participate in research among many Native communities. In recent years, researchers have made progress toward engaging in ethical health disparities research by using a community-based participatory research (CBPR) framework to work in close partnership with community members throughout the research process. In this methodological process paper, we discuss the collaborative development of a quantitative survey aimed at understanding risk and protective factors for substance use among a sample of tribal members residing on a rural AI reservation with numerous systems-level barriers to recovery and limited access to treatment. By using a CBPR approach and prioritizing trust and transparency with community partners and participants, we were able to successfully recruit our target sample and collect quality data from nearly 200 tribal members who self-identified as having a substance use problem. Strategies for enhancing buy-in and recruiting a community sample are discussed.

Skewes|Monica C|MC|0000-0001-9362-9825
Gonzalez|Vivian M|VM|
Gameon|Julie A|JA|
FireMoon|Paula|P|
Salois|Emily|E|
Rasmus|Stacy M|SM|
Lewis|Jordan P|JP|
Gardner|Scott A|SA|
Ricker|Adriann|A|
Reum|Martel|M|

D000086562:American Indians or Alaska Natives

Substance use
Community-based participatory research
Process
American Indian/Alaska Native
Methods


Eight Weeks of Plyometric Training Improves Ability to Change Direction and Dynamic Postural Control in Female Basketball Players.

Abstract: The aim of this study was to examine the effects of 8 weeks of plyometric training on the ability to change direction and postural control in female basketball players. 25 national level female basketball players aged 18-27 years participated in the study. Volunteers were randomly assigned to an experimental group (n = 13) who replaced a part of their standard regimen by plyometric training twice weekly for 8 weeks, and a control group (n = 12) who continued their usual in-season training program. Before and after the intervention, the ability to change direction and postural control were assessed by force platform under both static and dynamic conditions (with the eyes open and then closed). Isokinetic testing was also performed to calculate the Hamstring/Quadriceps (H/Q) strength ratio. The intervention improved ability to change direction (p ≤ 0.001, d = 1.51) and shortened path length (p = 0.038, d = 0.937) during static balance testing. However, it did not yield significant inter-group differences in postural control in the antero-posterior plane. The stance in the medio-lateral plane seemed the most responsive to the intervention, with reductions in surface area (p = 0.012, d = 0.285), velocity with the eyes closed (p = 0.031, d = 0.968), and path length with the eyes open (p = 0.029, d = 0.968). The intervention did not change the H/Q ratio at the two speeds tested (60° and 120°.s-1). In summary, the addition of 8 weeks plyometric training to the usual in-season basketball regimen of top-level female basketball players enhanced their ability to change direction and reduced the risk of falls and injuries by improving postural control, but did not increase the H/Q measure of knee stability.

Cherni|Yosser|Y|
Jlid|Mohamed Chedly|MC|
Mehrez|Hammami|H|
Shephard|Roy J|RJ|
Paillard|Thierry|T|
Chelly|Mohamed Souhaiel|MS|
Hermassi|Souhail|S|

balance
change of direction
hamstring/quadriceps ratio
stretch-shortening cycle
team sports


Secure Utilization of Beacons and UAVs in Emergency Response Systems for Building Fire Hazard.

Abstract: An intelligent emergency system for hazard monitoring and building evacuation is a very important application area in Internet of Things (IoT) technology. Through the use of smart sensors, such a system can provide more vital and reliable information to first-responders and also reduce the incidents of false alarms. Several smart monitoring and warning systems do already exist, though they exhibit key weaknesses such as a limited monitoring coverage and security, which have not yet been sufficiently addressed. In this paper, we propose a monitoring and emergency response method for buildings by utilizing beacons and Unmanned Aerial Vehicles (UAVs) on an IoT security platform. In order to demonstrate the practicability of our method, we also implement a proof of concept prototype, which we call the UAV-EMOR (UAV-assisted Emergency Monitoring and Response) system. Our UAV-EMOR system provides the following novel features: (1) secure communications between UAVs, smart sensors, the control server and a smartphone app for security managers; (2) enhanced coordination between smart sensors and indoor/outdoor UAVs to expand real-time monitoring coverage; and (3) beacon-aided rescue and building evacuation.

monitoring and emergency response systems


A systematic review of surgical procedures on thoracic myelopathy.

Abstract:
PURPOSE
The surgical treatment of thoracic myelopathy is still controversial and also a challenge for spine surgeons. Therefore, the objective of this study was to review the related literature on the surgical treatment of thoracic myelopathy and try to define treatment guidelines for spine surgeons on thoracic myelopathy.

METHODS
Relevant literatures were searched based on the PubMed, EMBASE, and Cochrane Library between January 2008 and December 2018. Some data on the characteristics of patients were extracted, including number of patients, mean age, surgical procedures, blood loss, complications, and pre-/post-operation modified JOA score. Recovery rate was used to assess the effect of surgery outcome, and the safety was evaluated by blood loss and incidence of complications.

RESULTS
Thirty-five studies met the inclusion criteria and were retrieved. A total of 2183 patients were included in our systematic review, with the average age of 55.2 years. There were 69.8% patients diagnosed as ossification of ligamentum flavum (OLF), 20.0% as ossification of posterior longitudinal ligament (OPLL), 9.3% as disk herniation (DH), and 0.9% as others including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS). The volume of blood loss was more in the treatment of circumferential decompression (CD) than posterior decompression (PD), and the incidence of complications was higher in CD (P < 0.05). The volume of blood loss in minimally invasive surgery (MIS) was lowest and the incidence of complications was 19.2%. Post-operation recovery rate was 0.49 in PD, 0.35 in CD, and 0.29 in MIS while the recovery rate was 0.54 in PD, 0.55 in CD, and 0.49 in MIS at the last follow-up. When focusing on the OLF specifically, incidence of complications in PD was much lower than CD, with less blood loss and higher recovery rate. Focusing on the OPLL specifically, incidence of complications in PD was much lower than CD, with less blood loss while there was no statistical difference in recovery rate between these two methods.

CONCLUSIONS
This systematic review showed that posterior decompression for thoracic myelopathy is safer and better than circumferential decompression according to the complication rate and surgical outcome. And we should also consider the location of compression before the operation.

D017887:Ossification of Posterior Longitudinal Ligament

Ossification of posterior longitudinal ligament (OPLL)


In Silico Prediction of Cytochrome P450-Drug Interaction: QSARs for CYP3A4 and CYP2C9.

Abstract: Cytochromes P450 (CYP) are the main actors in the oxidation of xenobiotics and play a crucial role in drug safety, persistence, bioactivation, and drug-drug/food-drug interaction. This work aims to develop Quantitative Structure-Activity Relationship (QSAR) models to predict the drug interaction with two of the most important CYP isoforms, namely 2C9 and 3A4. The presented models are calibrated on 9122 drug-like compounds, using three different modelling approaches and two types of molecular description (classical molecular descriptors and binary fingerprints). For each isoform, three classification models are presented, based on a different approach and with different advantages: (1) a very simple and interpretable classification tree; (2) a local (k-Nearest Neighbor) model based classical descriptors and; (3) a model based on a recently proposed local classifier (N-Nearest Neighbor) on binary fingerprints. The salient features of the work are (1) the thorough model validation and the applicability domain assessment; (2) the descriptor interpretation, which highlighted the crucial aspects of P450-drug interaction; and (3) the consensus aggregation of models, which largely increased the prediction accuracy.

Nembri|Serena|S| Grisoni|Francesca|F| Consonni|Viviana|V| Todeschini|Roberto|R|

D065688:Cytochrome P-450 CYP2C9 Inhibitors

D065692:Cytochrome P-450 CYP3A Inhibitors

in silico
QSAR
CYP3A4
CYP2C9
cytochrome P450
ADMET


Quantifying maladaptation during the evolution of sexual dimorphism.

Abstract: Females and males have distinct trait optima, resulting in selection for sexual dimorphism. However, most traits have strong cross-sex genetic correlations, which constrain evolutionary divergence between the sexes and lead to protracted periods of maladaptation during the evolution of sexual dimorphism. While such constraints are thought to be costly in terms of individual and population fitness, it remains unclear how severe such costs are likely to be. Building upon classical models for the 'cost of selection' in changing environments (sensu Haldane), we derived a theoretical expression for the analogous cost of evolving sexual dimorphism; this cost is a simple function of genetic (co)variances of female and male traits and sex differences in trait optima. We then conducted a comprehensive literature search, compiled quantitative genetic data from a diverse set of traits and populations, and used them to quantify costs of sexual dimorphism in the light of our model. For roughly 90% of traits, costs of sexual dimorphism appear to be modest, and comparable to the costs of fixing one or a few beneficial substitutions. For the remaining traits (approx. 10%), sexual dimorphism appears to carry a substantial cost-potentially orders of magnitude greater than costs of selection during adaptation to environmental changes.

Matthews|Genevieve|G|
Hangartner|Sandra|S|
Chapple|David G|DG|
Connallon|Tim|T|

cross-sex genetic correlation
cost of selection
sexual antagonism
sexual conflict
trade-off


Kinematics and EMG activity in Reverse Total Shoulder Arthroplasty.

Abstract:
Introduction
Patients undergoing a Reverse Total Shoulder Arthroplasty (RTSA) often have functional limitations that affect the range of motion of the shoulder. These limitations are not mechanical in nature, but instead linked to a reduced ability to generate muscle force. The specific aims of this study was to offer a comparison between the muscle activity generated by a post-operative RTSA shoulder in a patient to that of their contralateral shoulder during a series of functional activities.

Material & methods
A convenience sample of 10 subjects between the ages of 50-75 years of age were recruited. EMG and kinematic data were concomitantly collected while subjects completed tasks that included common activities of daily living.

Results
The main findings of this study were that all sub regions of the deltoid functioned as abductors, versus the native shoulder where the middle deltoid primarily works in abduction. For the scapular elevation activity there was a significant difference in flexion between the surgical and contralateral shoulder (p < .001), with the surgical shoulder having nearly 30° less range of motion.

Conclusion
Anticipating limitations in functional outcomes and range of motion for patients after RTSA may inform patient decision-making and improve clinical evaluations. The finding of increased mid deltoid function during lifting activity has implications for rehabilitation and encouraging protocols that strengthen the deltoid in concentric motions. Additionally, the decreased scapular elevation found in this study may guide rehabilitation focusing on regaining range of motion post-operatively.

Smith|Ryan A|RA|
Woolley|Katherine|K|
Mazzocca|Augustus|A|
Feinn|Richard|R|
Cote|Mark|M|
Gomlinski|Gregg|G|
Garbalosa|Juan|J|
Myrick|Karen M|KM|

Kinematics
EMG
Reverse total shoulder arthroplasty
Functional activity
Patient outcomes


Assessment of automatic associations with bodily sensations and agoraphobic situations in panic disorder.

Abstract:
BACKGROUND AND OBJECTIVES
One of the central assumptions of cognitive models of Panic Disorder (PD) is that automatic panic-related associations are a core feature of PD. However, empirical findings are mixed and inconsistent, rendering it difficult to evaluate the role of panic-related associations adequately, particularly in relation to the relevant theories. The present study aimed to further advance our understanding of automatic associations in PD, and therefore applied a paradigm novel in this context, namely an Extrinsic Affective Simon Task (EAST).

METHODS
Participants involved treatment seeking, unmedicated panic patients (n = 45) and healthy controls (n = 38). The EAST was applied prior to treatment. It included the following stimuli as targets: panic-related bodily sensations and agoraphobia-related situations, and as attributes: pleasant versus unpleasant, fear-related words.

RESULTS
Contrary to our expectations, panic patients did not show stronger negative than positive automatic associations for either panic-related symptoms or agoraphobia-related situations, compared to healthy controls. Moreover, EAST effects did not correlate with panic-related self-report measures.

LIMITATIONS
Although the present study involved patients who were actively seeking treatment, panic-related associations might not have been activated sufficiently. Hence, a brief activation procedure (e.g., hyperventilation) might have been needed to optimize the assessment condition.

CONCLUSIONS
The present findings do not support contemporary theories of panic-related associations. Therefore, follow-up work is needed to disentangle their functional and operational properties more thoroughly.

Woud|Marcella L|ML|
Becker|Eni S|ES|
Rinck|Mike|M|
Harmer|Catherine J|CJ|
Reinecke|Andrea|A|

D011569:Psychiatric Status Rating Scales

Automatic associations
Panic disorder
Extrinsic affective simon task (EAST)
Anxiety
Information processing bias


Sex Steroids Mediate Bidirectional Interactions Between Hosts and Microbes.

Abstract: The outcome of microbial infections in mammals, including humans, is affected by the age, sex, and reproductive status of the host suggesting a role for sex steroid hormones. Testosterone, estradiol, and progesterone, signaling through their respective steroid receptors, affect the functioning of immune cells to cause differential susceptibility to parasitic, bacterial, and viral infections. Microbes, including fungi, bacteria, parasites, and viruses, can also use sex steroid hormones and manipulate sex steroid receptor signaling mechanisms to increase their own survival and replication rate. The multifaceted use of sex steroid hormones by both microbes and hosts during infection forms the basis of this review. In the arms race between microbes and hosts, both hosts and microbes have evolved to utilize sex steroid hormone signaling mechanisms for survival.

Vom Steeg|Landon G|LG|
Klein|Sabra L|SL|

testosterone progesterone parasites estrogen influenza malaria toxoplasma


The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition "Killing Two Birds with One Stone"?

Abstract: Nuclear factor-κB (NF-κB) is a transcription factor that regulates the expression of various genes involved in inflammation and the immune response. The activation of NF-κB occurs via two pathways: inflammatory cytokines, such as TNF-α and IL-1β, activate the "classical pathway", and cytokines involved in lymph node formation, such as CD40L, activate the "alternative pathway". NF-κB1 (p50) and NF-κB2 (p52) double-knockout mice exhibited severe osteopetrosis due to the total lack of osteoclasts, suggesting that NF-κB activation is required for osteoclast differentiation. These results indicate that NF-κB may be a therapeutic target for inflammatory bone diseases, such as rheumatoid arthritis and periodontal disease. On the other hand, mice that express the dominant negative form of IκB kinase (IKK)-β specifically in osteoblasts exhibited increased bone mass, but there was no change in osteoclast numbers. Therefore, inhibition of NF-κB is thought to promote bone formation. Taken together, the inhibition of NF-κB leads to "killing two birds with one stone": it suppresses bone resorption and promotes bone formation. This review describes the role of NF-κB in physiological bone metabolism, pathologic bone destruction, and bone regeneration.

NF-κB inflammation osteoclasts osteoblasts


Outcomes of benign meningioma in older patients in the United States.

Abstract:
PURPOSE
Older patients have inferior outcomes for meningioma and experience more post-operative complications. The purpose of this study was to identify national treatment patterns and outcomes based on age for benign meningiomas using the National Cancer Database (NCDB).

MATERIAL AND METHODS
The NCDB was queried for patients with biopsy-proven World Health Organization Grade (WHO) grade I meningioma diagnosed between 2004 and 2015. Patients were stratified based on age: 18-50, 51-60, 61-70, 71-80, and > 80 years of age. Clinicodemographic details were compared via the Chi Square test. Multivariable logistic regression was used to determine factors associated with receipt of treatment and post-operative complications. Multivariable Cox regression and the Kaplan-Meier method were used to examine survival.

RESULTS
56,960 patients met inclusion criteria with a median follow-up of 48 months. Ages 61-70 (OR 0.73, 95% CI 0.62-0.85, p < .001), ages 71-80 (OR 0.51, 95% CI 0.43-0.60, p < .001), and age > 80 (0.16, 95% CI 0.14-0.19, p < .001) were less likely to receive treatment. Older age groups were associated with increased risk of post-operative complications and post-operative complications predicted for decreased survival. Treatment with surgery (HR 0.57, 95% CI 0.52-0.62, p < .001) and surgery and radiation (HR 0.59, 95% CI 0.50-0.70, p < .001) provided a survival benefit. Older age was associated with a survival decrement.

CONCLUSIONS
Older patients are less likely to undergo treatment for benign meningioma and are more likely to have post-operative complications. Survival decreased with increasing age. Treatment improved survival among all patients. Risk-benefit ratio of treatment should be carefully considered when treating older patients with benign meningioma.

Albert|Ashley|A|
Lee|Anna|A|
Thomas|Toms Vengaloor|TV|
Vijayakumar|Srinivasan|S|

D000368:Aged
D000369:Aged, 80 and over
D006801:Humans
D053208:Kaplan-Meier Estimate
D008577:Meningeal Neoplasms
D008579:Meningioma
D018714:Radiotherapy, Adjuvant
D012189:Retrospective Studies
D014481:United States

Benign meningioma
Older patients
Surgery
Radiation


R705H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17.

Abstract: MYH9-related disease (MYH9-RD) is a rare autosomal dominant disease caused by mutation of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). MYH9-RD patients have macrothrombocytopenia and granulocyte inclusions (pathognomonic sign of the disease) containing wild-type and mutant NMMHC-IIA. During life they might develop sensorineural hearing loss, cataract, glomerulonephritis, and elevation of liver enzymes. One of the MYH9 mutations, p.R705H, was previously reported to be associated with DFNA17, an autosomal dominant non-syndromic sensorineural hearing loss without any other features associated. We identified the same mutation in two unrelated families, whose four affected individuals had not only hearing impairment but also thrombocytopenia, giant platelets, leukocyte inclusions, as well as mild to moderate elevation of some liver enzymes. Our data suggest that DFNA17 should not be a separate genetic entity but part of the wide phenotypic spectrum of MYH9-RD characterized by congenital hematological manifestations and variable penetrance and expressivity of the extra-hematological features.

Verver|E|E|
Pecci|A|A|
De Rocco|D|D|
Ryhänen|S|S|
Barozzi|S|S|
Kunst|H|H|
Topsakal|V|V|
Savoia|A|A|

DFNA17 non-syndromic sensorineural hearing loss


Plasma Biomarkers of Human Immunodeficiency Virus-Related Systemic Inflammation and Immune Activation in Sub-Saharan Africa Before and During Suppressive Antiretroviral Therapy.

Abstract: We evaluated immune biomarker profiles in human immunodeficiency virus (HIV)-infected adults (n = 398) from 5 African countries. Although all biomarkers decreased after antiretroviral therapy (ART) initiation, levels of C-X-C chemokine ligand 10 (CXCL10), lipopolysaccharide-binding protein, C-reactive protein, soluble CD163, and soluble scavenger receptor CD14 were significantly higher during ART than in an HIV-uninfected reference group (n = 90), indicating persistent monocyte/macrophage activation, inflammation, and microbial translocation. Before ART initiation, high HIV viral load was associated with elevated CXCL10 and tuberculosis coinfection was associated with elevated soluble CD14. High pre-ART levels of each biomarker strongly predicted residual immune activation during ART. Chemokine (C-C motif) ligand 2, lipopolysaccharide-binding protein, C-reactive protein, and interleukin 6 were differentially expressed between countries. Further research is needed on the clinical implications of residual immune dysregulation.

Kroeze|Stefanie|S|
Wit|Ferdinand W|FW|
Rossouw|Theresa M|TM|
Steel|Helen C|HC|
Kityo|Cissy M|CM|
Siwale|Margaret|M|
Akanmu|Sulaimon|S|
Mandaliya|Kishor|K|
de Jager|Marleen|M|
Ondoa|Pascale|P|
Reiss|Peter|P|
Rinke de Wit|Tobias F|TF|
Kootstra|Neeltje|N|
Hamers|Raph L|RL|

biomarkers
inflammation
immune activation
sub-Saharan Africa
antiretroviral therapy
HIV


Application of failure mode and effects analysis to reduce microplastic emissions.

Abstract: A complete understanding of the occurrence of microplastics and the methods to eliminate their sources is an urgent necessity to minimize the pollution caused by microplastics. The use of plastics in any form releases microplastics to the environment. Existing policy instruments are insufficient to address microplastics pollution and regulatory measures have focussed only on the microbeads and single-use plastics. Fees on the use of plastic products may possibly reduce their usage, but effective management of plastic products at their end-of-life is lacking. Therefore, in this study, the microplastic-failure mode and effect analysis (MP-FMEA) methodology, which is a semi-qualitative approach capable of identifying the causes and proposing solutions for the issue of microplastics pollution, has been proposed. The innovative feature of MP-FMEA is that it has a pre-defined failure mode, that is, the release of microplastics to air, water and soil (depending on the process) or the occurrence of microplastics in the final product. Moreover, a theoretical recycling plant case study was used to demonstrate the advantages and disadvantages of this method. The results revealed that MP-FMEA is an easy and heuristic technique to understand the failure-effect-causes and solutions for reduction of microplastics and can be applied by researchers working in different domains apart from those relating to microplastics. Future studies can include the evaluation of the use of MP-FMEA methodology along with quantitative methods for effective reduction in the release of microplastics.

D000067495:Healthcare Failure Mode and Effect Analysis

Microplastic–failure mode and effect analysis


Molecular mechanism and therapy application of necrosis during myocardial injury.

Abstract: Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new pharmacological application in the treatment of heart diseases. In this review, we summarize the advanced progress in these signalling pathways and discuss the pathos-physiological relevance and therapeutic implication of targeting necrosis in heart diseases treatment.

Xu|Tao|T|0000-0003-1698-5556
Ding|Wei|W|
Tariq|Muhammad Akram|MA|
Wang|Yu|Y|
Wan|Qinggong|Q|
Li|Mengyang|M|0000-0003-1491-4105
Wang|Jianxun|J|

therapy application
programmed necrosis
heart diseases
death receptor pathway
mitochondrial pathway


Evolution of the Public Health Preparedness and Response Capability Standards to Support Public Health Emergency Management Practices and Processes.

Abstract: In spring 2011, the Centers for Disease Control and Prevention (CDC) released Public Health Preparedness Capabilities: National Standards for State and Local Planning. The capability standards provide a framework that supports state, local, tribal, and territorial public health agency preparedness planning and response to public health threats and emergencies. In 2017, a project team at the CDC Division of State and Local Readiness incorporated input from subject matter experts, national partners, and stakeholders to update the 2011 capability standards. As a result, CDC released the updated capability standards in October 2018, which were amended in January 2019. The original structure of the 15 capability standards remained unchanged, but updates were made to capability functions, tasks, and resource elements to reflect advances in public health emergency preparedness and response practices since 2011. When the number of functions and tasks in the 2018 capability standards were compared to those in the 2011 capabilities, only 20% (3/15) of the capabilities had a decrease in function number. The majority of changes were at the task level (task numbers changed in 80%, or 12/15, capabilities) in the 2018 version. The capability standards provide public health agencies with a practical framework, informed by updated science and tools, which can guide prioritization of limited resources to strengthen public health agency emergency preparedness and response capacities.

Martinez|DeAndrea|D| Talbert|Todd|T| Romero-Steiner|Sandra|S| Kosmos|Christine|C| Redd|Stephen|S|

D002487:Centers for Disease Control and Prevention, U.S.

Emergency medicine
Emergency planning
Public health preparedness/response


Standardized Clinical Assessment And Management Plans (SCAMPs) provide a better alternative to clinical practice guidelines.

Abstract: Variability in medical practice in the United States leads to higher costs without achieving better patient outcomes. Clinical practice guidelines, which are intended to reduce variation and improve care, have several drawbacks that limit the extent of buy-in by clinicians. In contrast, standardized clinical assessment and management plans (SCAMPs) offer a clinician-designed approach to promoting care standardization that accommodates patients' individual differences, respects providers' clinical acumen, and keeps pace with the rapid growth of medical knowledge. Since early 2009 more than 12,000 patients have been enrolled in forty-nine SCAMPs in nine states and Washington, D.C. In one example, a SCAMP was credited with increasing clinicians' rate of compliance with a recommended specialist referral for children from 19.6 percent to 75 percent. In another example, SCAMPs were associated with an 11-51 percent decrease in total medical expenses for six conditions when compared with a historical cohort. Innovative tools such as SCAMPs should be carefully examined by policy makers searching for methods to promote the delivery of high-quality, cost-effective care.

Farias|Michael|M|
Jenkins|Kathy|K|
Lock|James|J|
Rathod|Rahul|R|
Newburger|Jane|J|
Bates|David W|DW|
Safran|Dana G|DG|
Friedman|Kevin|K|
Greenberg|Josh|J|

Variations
Children’s Health
Evidence-Based Medicine
Health Reform
Organization And Delivery Of Care


Two phenolic antioxidants in Suoyang enhance viability of •OH-damaged mesenchymal stem cells: comparison and mechanistic chemistry.

Abstract:
BACKGROUND
Suoyang originates from a psammophyte named Cynomorium songaricum Rupr and has been known as a phenolic-antioxidant-enriched traditional Chinese herbal medicine. The present study attempted to investigate the protective effect of phenolic antioxidants in Suoyang towards •OH-mediated MSCs and then further discusses the chemical mechanisms.

METHODS
The lyophilized aqueous extract of Suoyang (LAS) was prepared and characterized using HPLC. Then, two phenolic antioxidant references, epicatechin and luteolin-7-O-β-D-glucoside, along with LAS, were investigated for their effects on the viability of •OH-treated MSCs using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The comparison and mechanistic chemistry of epicatechin and luteolin-7-O-β-D-glucoside were further explored using various antioxidant assays, including PTIO•-scavenging, FRAP (ferric ion reducing antioxidant power), ABTS+•-scavenging, and DPPH•-scavenging. Their Fe2+-binding capacities were also compared using ultraviolet (UV) spectra.

RESULTS
The HPLC analysis indicated that there are 8 phenolic antioxidants in LAS, including epicatechin, luteolin-7-O-β-D-glucoside, gallic acid, protocatechuic acid, catechin, isoquercitrin, phlorizin, and naringenin. The MTT assay revealed that epicatechin could more effectively increase the survival of •OH-treated MSCs than luteolin-7-O-β-D-glucoside. Similarly, epicatechin exhibited higher antioxidant abilities than luteolin-7-O-β-D-glucoside in the DPPH•-scavenging, ABTS+•-scavenging, FRAP, and PTIO•-scavenging assays. In the Fe2+-binding assay, luteolin-7-O-β-D-glucoside gave a stronger UV peak at 600 nm, with ε = 2.62 × 106 M-1 cm-1, while epicatechin produced two peaks at 450 nm (ε = 8.47 × 105 M-1 cm-1) and 750 nm (ε = 9.68 × 105 M-1 cm-1).

CONCLUSION
As two reference antioxidants in Suoyang, epicatechin and luteolin-7-O-β-D-glucoside can enhance the viability of •OH-damaged MSCs. Such a beneficial effect may be from their antioxidant effects, including direct-antioxidant and indirect-antioxidant (i.e., Fe2+-binding) processes. In the direct-antioxidant process, proton (H+), one electron (e), or even hydrogen-atom (•H) transfer may occur to fulfill radical-scavenging (especially •OH-scavenging); in this aspect, epicatechin is superior to luteolin-7-O-β-D-glucoside due to the presence of more phenolic -OHs. The additional -OHs can also be responsible for the better cytoprotective effect. In terms of indirect-antioxidant potential, however, epicatechin is inferior to luteolin-7-O-β-D-glucoside due to the absence of a hydroxyl-keto moiety. These findings will provide new information about medicinal psammophytes for MSC transplantation.

Phenolic antioxidants
Suoyang
Mesenchymal stem cells
Epicatechin
Luteolin-7-O-β-D-glucoside


Curcumin nanoparticles inhibit corneal neovascularization.

Abstract:
UNLABELLED
Corneal neovascularization is a leading cause for compromised vision. Therapeutic prevention of corneal neovascularization is a major clinical challenge, and there is a compelling need to seek effective and safe therapy for this pathology. This study is aimed to evaluate curcumin nanoparticle for prevention of corneal neovascularization. MePEG-PCL nanoparticles were successfully prepared and characterized. The nanoparticle of curcumin has shown increased efficiency in preventing angiogenic sprouting in vitro. Topical delivery of curcumin nanoparticle in the eye showed enhanced retention of curcumin in the cornea, and significant improvement in prevention of corneal neovascularization over free curcumin as graded clinically and by histopathology; suppression in the expression of VEGF, inflammatory cytokines, and MMP was evidenced in the treated cornea. Curcumin inhibited NFκB in LPS-induced corneal cells. Histopathology and scanning electron microscopy showed absence of any adverse change in the corneal structure following application of curcumin nanoparticle. Therefore, we conclude that curcumin nanoparticle can be a potential candidate for prevention of corneal neovascularization.

KEY MESSAGE
• Curcumin nanoparticles show enhanced retention of curcumin in the cornea. • Curcumin NPs suppress the expression of VEGF, inflammatory cytokines, and MMP. • Curcumin NPs prevent corneal neovascularization by suppressing the NFκB pathway. • Curcumin NPs may be a promising candidate for prevention of corneal neovascularization.

Pradhan|Nirparaj|N| Guha|Rajdeep|R| Chowdhury|Sushovan|S| Nandi|Sudip|S| Konar|Aditya|A| Hazra|Sarbani|S|

D042461:Vascular Endothelial Growth Factor A


Mechanical and cytotoxicity evaluation of nanostructured hydroxyapatite-bredigite scaffolds for bone regeneration.

Abstract: Despite the attractive characteristics of three-dimensional pure hydroxyapatite (HA) scaffolds, due to their weak mechanical properties, researches have focused on the development of composite scaffolds via introducing suitable secondary components. The aim of this study was to develop, for the first time, three-dimensional HA-bredigite (Ca7MgSi4O16) scaffolds containing various amounts of bredigite nanopowder (0, 5, 10 and 15wt.%) using space holder technique. Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction spectroscopy were applied in order to study the morphology, fracture surface and phase compositions of nanopowders and scaffolds. Furthermore, the effects of scaffold composition on the mechanical properties, bioactivity, biodegradability, and cytotoxicity were also evaluated. Results showed that the composite scaffolds with average pore size in the range of 220-310μm, appearance porosity of 63.1-75.9% and appearance density of 1.1±0.04g/cm(3) were successfully developed, depending on bredigite content. Indeed, the micropore size of the scaffolds reduced with increasing bredigite content confirming that the sinterability of the scaffolds was improved. Furthermore, the compression strength and modulus of the scaffolds significantly enhanced via incorporation of bredigite content from 0 to 15wt.%. The composite scaffolds revealed superior bioactivity and biodegradability with increasing bredigite content. Moreover, MTT assay confirmed that HA-15wt.% bredigite scaffold significantly promoted cell proliferation compared to tissue culture plate (control) and HA scaffold. Based on these results, three-dimensional HA-bredigite scaffolds could be promising replacements for HA scaffolds in bone regeneration.

Eilbagi|Marjan|M| Emadi|Rahmatollah|R| Raeissi|Keyvan|K| Kharaziha|Mahshid|M| Valiani|Ali|A|

D017636:Asbestos, Amphibole
D001861:Bone Regeneration
D018786:Bone Substitutes
D045744:Cell Line, Tumor
D004353:Drug Evaluation, Preclinical
D017886:Durapatite
D006801:Humans
D049329:Nanostructures
D054457:Tissue Scaffolds

Cytotoxicity
Hydroxyapatite
Mechanical properties
Bredigite
Three-dimensional scaffolds


Clinical Outcomes and Prevalence of Hepatitis E Virus (HEV) Among Non-A-C Hepatitis Patients in Egypt.

Abstract:
Background
Hepatitis E virus (HEV) is an emerging infectious agent that causes acute hepatitis in developing and developed countries. Diagnosis of HEV infection has not been routinely done in Egyptian hospitals, and clinicians do not prescribe ribavirin (RBV) for acute hepatitis cases of unknown etiology (AHUE). We aimed to screen patients with AHUE for the presence of HEV markers and to determine the complications associated with HEV infection.

Patients and Methods
HEV markers (anti-HEV IgM, anti-HEV IgG, and HEV RNA) were assessed in patients with AHUE (n=300) admitted to Assiut University Hospitals. RT-qPCR was used to detect the viral load and sequencing analysis was carried out to determine the genotype of the detected viruses. Phylogenetic tree was constructed to evaluate the genetic relatedness between the isolates. Laboratory parameters and the outcomes of infection were determined.

Results
Acute HEV infection (AHE) was detected in 30 out of 300 (10%) of AHUE patients. Anti-HEV IgM, HEV RNA, and anti-HEV IgG were reported in 83%, 50%, and 43% of the samples, respectively. HEV RNA load ranged from 5×102 IU/mL to 1.1×104 IU/mL. Sequencing of the isolated viruses revealed that five viruses belong to HEV-1 and one isolate belongs to HEV-3 with high homology to the virus recently isolated from the cow and goat milk in the Egyptian villages. Although previous reports showed that attenuated HEV isolates were circulating in Egypt, four out of 30 patients (13%) developed coagulopathy and hepatic encephalopathy and died due to fulminant hepatic failure (FHF) within 3-6 weeks of hospitalization. Age, malignancy, and a history of pre-existing liver diseases were a risky factor for FHF development.

Conclusion
AHE is common in Upper Egypt. Older patients with malignancy and/or a history of liver diseases are risky. HEV diagnosis and treatment become pivotal in Egyptian hospitals to reduce the fatality rate and they should start urgently and promptly.

Egypt
diagnosis
ribavirin
fulminant hepatitis failure
acute hepatitis E


Ketamine as Part of a Multimodal Approach to Postoperative Pain Management.

Abstract: Some surgeries present increased challenges for adequate perioperative pain management, which require innovative methods to prevent development of chronic postsurgical pain (CPSP). Ketamine is an adjunct to traditional pain management methods and is an effective analgesic. The potent antihyperalgesic effects of ketamine represent an interesting option for those searching for multimodal approaches. This case report describes pain management for a 73-year old man scheduled for surgical excision of a sacral chordoma who was at high risk of development of CPSP. The intraoperative pain management plan consisted of T9-10 epidural anesthesia with continuous infusion of ropivacaine and hydromorphone, intravenous low-dose ketamine infusion, and intermittent intravenous hydromorphone boluses for breakthrough pain. Post-operatively the epidural infusion was continued for 4 days. The ketamine infusion rate was decreased on transfer to the intensive care unit and titrated to off by postoperative day 3. An intravenous hydromorphone patient-controlled analgesia pump was available to the patient for breakthrough pain postoperatively. This multimodal approach controlled the patient's pain postoperatively without reported complications. At his 1-year postsurgical follow-up visit, the patient reported some generalized "dull aching pain" that was well controlled with oral ibuprofen. Overall, the patient was satisfied with his pain control, and CPSP did not develop.

ketamine
postoperative pain management
Chronic postsurgical pain
sacral chordoma


Probing Genome Maintenance Functions of human RECQ1.

Abstract: The RecQ helicases are a highly conserved family of DNA-unwinding enzymes that play key roles in protecting the genome stability in all kingdoms of life. Human RecQ homologs include RECQ1, BLM, WRN, RECQ4, and RECQ5β. Although the individual RecQ-related diseases are characterized by a variety of clinical features encompassing growth defects (Bloom Syndrome and Rothmund Thomson Syndrome) to premature aging (Werner Syndrome), all these patients have a high risk of cancer predisposition. Here, we present an overview of recent progress towards elucidating functions of RECQ1 helicase, the most abundant but poorly characterized RecQ homolog in humans. Consistent with a conserved role in genome stability maintenance, deficiency of RECQ1 results in elevated frequency of spontaneous sister chromatid exchanges, chromosomal instability, increased DNA damage and greater sensitivity to certain genotoxic stress. Delineating what aspects of RECQ1 catalytic functions contribute to the observed cellular phenotypes, and how this is regulated is critical to establish its biological functions in DNA metabolism. Recent studies have identified functional specialization of RECQ1 in DNA repair; however, identification of fundamental similarities will be just as critical in developing a unifying theme for RecQ actions, allowing the functions revealed from studying one homolog to be extrapolated and generalized to other RecQ homologs.

RecQ
Helicase
DNA damage
DNA repair
genomic instability


Igloo-Plot: a tool for visualization of multidimensional datasets.

Abstract: Advances in science and technology have resulted in an exponential growth of multivariate (or multi-dimensional) datasets which are being generated from various research areas especially in the domain of biological sciences. Visualization and analysis of such data (with the objective of uncovering the hidden patterns therein) is an important and challenging task. We present a tool, called Igloo-Plot, for efficient visualization of multidimensional datasets. The tool addresses some of the key limitations of contemporary multivariate visualization and analysis tools. The visualization layout, not only facilitates an easy identification of clusters of data-points having similar feature compositions, but also the 'marker features' specific to each of these clusters. The applicability of the various functionalities implemented herein is demonstrated using several well studied multi-dimensional datasets. Igloo-Plot is expected to be a valuable resource for researchers working in multivariate data mining studies. Igloo-Plot is available for download from: http://metagenomics.atc.tcs.com/IglooPlot/.

Kuntal|Bhusan K|BK|
Ghosh|Tarini Shankar|TS|
Mande|Sharmila S|SS|

Data mining
Algorithms
Multivariate analysis
Software


Genome-wide SNP discovery and population structure analysis in pepper (Capsicum annuum) using genotyping by sequencing.

Abstract:
BACKGROUND
Knowledge on population structure and genetic diversity in vegetable crops is essential for association mapping studies and genomic selection. Genotyping by sequencing (GBS) represents an innovative method for large scale SNP detection and genotyping of genetic resources. Herein we used the GBS approach for the genome-wide identification of SNPs in a collection of Capsicum spp. accessions and for the assessment of the level of genetic diversity in a subset of 222 cultivated pepper (Capsicum annum) genotypes.

RESULTS
GBS analysis generated a total of 7,568,894 master tags, of which 43.4% uniquely aligned to the reference genome CM334. A total of 108,591 SNP markers were identified, of which 105,184 were in C. annuum accessions. In order to explore the genetic diversity of C. annuum and to select a minimal core set representing most of the total genetic variation with minimum redundancy, a subset of 222 C. annuum accessions were analysed using 32,950 high quality SNPs. Based on Bayesian and Hierarchical clustering it was possible to divide the collection into three clusters. Cluster I had the majority of varieties and landraces mainly from Southern and Northern Italy, and from Eastern Europe, whereas clusters II and III comprised accessions of different geographical origins. Considering the genome-wide genetic variation among the accessions included in cluster I, a second round of Bayesian (K = 3) and Hierarchical (K = 2) clustering was performed. These analysis showed that genotypes were grouped not only based on geographical origin, but also on fruit-related features.

CONCLUSIONS
GBS data has proven useful to assess the genetic diversity in a collection of C. annuum accessions. The high number of SNP markers, uniformly distributed on the 12 chromosomes, allowed the accessions to be distinguished according to geographical origin and fruit-related features. SNP markers and information on population structure developed in this study will undoubtedly support genome-wide association mapping studies and marker-assisted selection programs.

Taranto|F|F| D'Agostino|N|N| Greco|B|B| Cardi|T|T| Tripodi|P|P|0000-0001-5429-3847

Population structure
Pepper
Genotyping by sequencing
Single nucleotide polymorphism


The evolution of selfing from outcrossing ancestors in Brassicaceae: what have we learned from variation at the S-locus?

Abstract: Evolutionary transitions between mating systems have occurred repetitively and independently in flowering plants. One of the most spectacular advances of the recent empirical literature in the field was the discovery of the underlying genetic machinery, which provides the opportunity to retrospectively document the scenario of the outcrossing to selfing transitions in a phylogenetic perspective. In this review, we explore the literature describing patterns of polymorphism and molecular evolution of the locus controlling self-incompatibility (S-locus) in selfing species of the Brassicaceae family in order to document the transition from outcrossing to selfing, a retrospective approach that we describe as the 'mating system genes approach'. The data point to strikingly contrasted scenarios of transition from outcrossing to selfing. We also perform original analyses of the fully sequenced genomes of four species showing self-compatibility, to compare the orthologous S-locus region with that of functional S-locus haplotypes. Phylogenetic analyses suggest that all species we investigated evolved independently towards loss of self-incompatibility, and in most cases almost intact sequences of either of the two S-locus genes suggest that these transitions occurred relatively recently. The S-locus region in Aethionema arabicum, representing the most basal lineage of Brassicaceae, showed unusual patterns so that our analysis could not determine whether self-incompatibility was lost secondarily, or evolved in the core Brassicaceae after the split with this basal lineage. Although the approach we detail can only be used when mating system genes have been identified in a clade, we suggest that its integration with phylogenetic and population genetic approaches should help determine the main routes of this predominant mating system shift in plants.

Vekemans|X|X|
Poux|C|C|
Goubet|P M|PM|
Castric|V|V|

D005075:Biological Evolution
D019607:Brassicaceae
D003433:Crosses, Genetic
D004251:DNA Transposable Elements
D017343:Genes, Plant
D049810:Genetic Speciation
D018745:Genome, Plant
D010802:Phylogeny
D012100:Reproduction, Asexual

selfing
S-locus
mating system
phylogenetics
self-incompatibility


Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction.

Abstract: The Prospective comparison of Angiotensin Receptor-neprilysin inhibitor (ARNI) with Angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and morbidity in Heart Failure (HF) trial (PARADIGM-HF) showed that adding a neprilysin inhibitor (sacubitril) to a renin-angiotensin system blocker (and other standard therapy) reduced morbidity and mortality in ambulatory patients with chronic HF with reduced ejection fraction (HFrEF). In PARADIGM-HF, valsartan combined with sacubitril (a so-called ARNI) was superior to the current gold standard of an ACEI, specifically enalapril, reducing the risk of the primary composite outcome of cardiovascular (CV) death or first HF hospitalization by 20% and all-cause death by 16%. Following the results of PARADIGM-HF, sacubitril/valsartan was approved by American and European regulatory authorities for the treatment of HFrEF. The burden of HF in Asia is substantial, both due to the huge population of the region and as a result of increasing CV risk factors and disease. Both the prevalence and mortality associated with HF are high in Asia. In the following review, we discuss the development of sacubitril/valsartan, the prototype ARNI, and the available evidence for its efficacy and safety in Asian patients with HFrEF.

Sacubitril/valsartan
Asians
Heart failure


Neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: a feasibility and safety study.

Abstract:
BACKGROUND
Standard treatment for colorectal peritoneal carcinomatosis typically involves cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and if possible, postoperative adjuvant chemotherapy. However, a substantial percentage of patients never receive adjuvant chemotherapy because of postoperative complications. Neoadjuvant chemotherapy could be beneficial in this setting, so we assessed its feasibility and safety when used before cytoreductive surgery and HIPEC.

METHODS
In this non-randomized, single-center, observational feasibility study, patients were scheduled to receive six cycles of capecitabine and oxaliplatin before cytoreductive surgery and HIPEC. Computed tomography was performed after the third and sixth chemotherapy cycles to evaluate tumor response, and patients underwent cytoreductive surgery and HIPEC if there were no pulmonary and/or hepatic metastases. Postoperative complications, graded according to the Clavien-Dindo classification, were compared with those of a historic control group that received postoperative adjuvant chemotherapy.

RESULTS
Of the 14 patients included in the study, 4 and 3 had to terminate neoadjuvant chemotherapy early because of toxicity and tumor progression, respectively. Cytoreductive surgery and HIPEC were performed in eight patients, and the timing and severity of complications were comparable to those of patients in the historic control group treated without neoadjuvant chemotherapy.

CONCLUSION
Patients with peritoneal metastases due to colorectal carcinoma can be treated safely with neoadjuvant chemotherapy before definitive therapy with cytoreductive surgery and HIPEC.

TRIAL REGISTRATION NUMBER
NTR 3905, registered on 20th march, 2013, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3905.

Leimkühler|M|M|
Hemmer|P H J|PHJ|
Reyners|A K L|AKL|
de Groot|D J A|DJA|
van Ginkel|R J|RJ|
Been|L B|LB|
de Bock|G H|GH|
van Leeuwen|B L|BL|

D000971:Antineoplastic Combined Chemotherapy Protocols

D010478:Chemotherapy, Cancer, Regional Perfusion

Neoadjuvant chemotherapy
Colorectal cancer
Peritoneal carcinomatosis
HIPEC


Nutritional status and personal hygiene practices of primary school children: A cross-sectional study from Meghalaya, India.

Abstract:
Background
Poor nutritional status in primary school children can lead to several health problems such as easy susceptibility to common childhood diseases. Personal hygiene status is an important predictor of nutritional status and morbidity in children as water- and sanitation-related diseases are the leading causes of early morbidity and mortality in children. The present study was conducted to assess the nutritional status as well as personal hygiene practices of primary school going children.

Method
The present study was a cross-sectional study conducted in selected urban and rural areas of Shillong in children 6-12 years of age. Two schools each from the rural and urban area were selected using simple random sampling. The total sample size calculated was 510. Height, weight, and BMI were taken for all the children following the standard procedures. WHO growth standards were used for grading of nutritional status. A questionnaire with scores was used for grading of personal hygiene status.

Results
The overall prevalence of underweight in the children of 6-9 years was 74 (18.7%) and that of stunting was 68 (17.2%). The overall prevalence of thinness and stunting in children aged 10-12 was 38 (19.1%) and 46 (23.2%). The prevalence of nutritional deficiency syndromes was 192 (32.4%). Regarding the personal hygiene status, it was observed that 65 (11%) had very good personal hygiene, 292 (49.3%) were labeled as good, 200 (33.8%) were average, and 35 (5.9%) had poor personal hygiene.

Conclusion
The primary school going children in Shillong had poor nutritional status but the majority of them had good personal hygiene practices. Mother's educational status played an important role in determining the nutritional and personal hygiene status of the children.

Bhattacharyya|Himashree|H|
Medhi|G K|GK|
Pala|Star|S|
Sarkar|Amrita|A|
Lynrah|Wallambok|W|
Kharmujai|Ophelia Mary|OM|


Coming of age in Roman Britain: Osteological evidence for pubertal timing.

Abstract:
OBJECTIVES
Puberty is a key transitional phase of the human life course, with important biological and social connotations. Novel methods for the identification of the pubertal growth spurt and menarche in skeletal remains have recently been proposed (Shapland and Lewis, 2013, 2014). In this study we applied the methods to two Romano-British cemetery samples (1st-early 5th centuries AD) in order to investigate the timing of puberty during this period and further assess the veracity of the methods.

MATERIALS AND METHODS
Shapland and Lewis' methods (2013, 2014) were applied to 38 adolescents (aged 8-20 years) from the British cemetery sites of Roman London (1st-early 5th centuries AD) and Queenford Farm, Oxfordshire (4th-early 5th centuries AD).

RESULTS
Overall, the Romano-British males and females experienced the onset of puberty at similar ages to modern European adolescents, but subsequently experienced a longer period of pubertal development. Menarche occurred between the ages of 15 and 17 years for these Romano-British females, around 2 to 4 years later than for present-day European females.

DISCUSSION
The observed Romano-British pattern of pubertal timing has various possible explanations, including exposure to environmental stressors in early urban environments. The pattern of pubertal timing is largely congruent with social age transitions alluded to in ancient texts and funerary evidence for this period. While there are limitations to the application of these techniques to archaeological samples, they were successfully applied in this study, and may have important implications for understandings of past life courses, as well as providing a long-term perspective on pubertal timing and biocultural interactions.

Arthur|Nichola A|NA|
Gowland|Rebecca L|RL|
Redfern|Rebecca C|RC|

growth spurt
menarche
adolescence
skeletal development


Electroacupuncture improves neuronal function by stimulation of ascending peripheral nerve conduction in rats with spinal cord injury.

Abstract:
OBJECTIVE
To establish a method of transient sciatic nerve blockade and to examine the involvement of the ascending peripheral nerve pathway in the therapeutic effect of electroacupuncture at Zusanli (ST 36) in rats with spinal cord injury (SCI).

METHODS
We examined the transient effect of daily lidocaine administration into the posteromedial part of the greater trochanter on sciatic nerve function using electrophysiological examination and histopathology of the sciatic nerve. Rats were divided into three groups: an SCI group (SCI without treatment), an SCI with electroacupuncture treatment (SCI-EA) group, and an SCI with nerve block and electroacupuncture (SCI-NB-EA) group (nerve block was achieved by lidocaine administration to transiently block the ascending peripheral nerve pathway). Behavioral tests and electrophysiological examinations were performed to evaluate recovery of neurological function.

RESULTS
Sciatic nerve conduction was normal immediately before daily lidocaine administration. Histopathological analysis also indicated normal sciatic nerve, confirming that lidocaine nerve blockade was suitable and reversible for transiently eliminating nerve transmission. Neurological function in the SCI-EA group was superior to that in the SCI group, while no differences were found between the SCI and SCI-NB-EA groups.

CONCLUSION
Electroacupuncture treatment can promote recovery of neurological function. Facilitation of nerve conduction may play an important role in this recovery.

Song|Meng|M| Okuno|Seiichi|S| Orito|Kensuke|K| Chen|Wu|W| Kamiie|Junichi|J|

Electroacupuncture
Nerve conduction
Spinal cord injuries
Lidocaine
Electrophysiology


Role of the Posterior Fat Pad Sign in Treating Displaced Extension Type Supracondylar Fractures of the Pediatric Elbow Using the Blount Method.

Abstract: The posterior fat pad sign (PFPS) on the lateral elbow X-ray is useful in the diagnosis of a suspected nondisplaced fracture about the elbow after a subtle injury. However, the presence of a PFPS hallmarks a continuous posterior periosteum-posterior capsule of the distal humerus. This anatomic structure is crucial for the stable anatomic reduction of a displaced extension type supracondylar fracture. Subsequently, the presence of a PFPS may predict the successful nonoperative treatment of a Gartland III-type fracture by means of the Blount method, implying less implant-related morbidity and less intraoperative radiation exposure for the patient and surgeon. Furthermore, it is concluded that a PFPS-positive displaced extension type supracondylar fracture is definitively classified as a Gartland III and not a Gartland IV-type fracture. A retrospective study of 75 displaced extension type supracondylar elbow fractures was performed. All fractures had an initial attempt at a closed reduction under general anesthesia. A stable reduction in 120 degrees of elbow flexion without vascular compromise of the affected limb was achieved in 45 fractures, which were splinted in this position. In the remaining 30 cases, fracture reduction was either inadequate or was achieved with excess elbow flexion, which impaired distal blood flow. These fractures were pinned percutaneously and splinted in 90 degrees of elbow flexion. The two treatment groups were retrospectively compared for the presence of a PFPS. The displaced extension type supracondylar fractures, which were treated successfully by the Blount method, had a statistically significant higher prevalence (chi-square-Yates =4.91, p<0.05) of a positive PFPS (28/45 patients, 62.22%) compared to the fractures treated by closed reduction and percutaneous pinning (10/30, 33.33%). No vascular complications were observed. The long-term outcome did not differ between groups.

Samelis|Panagiotis V|PV|
Papagrigorakis|Eftychios|E|
Ellinas|Sotiris|S|

fat pad supracondylar fracture elbow blount gartland paediatric


Humanoid robotics in health care: An exploration of children's and parents' emotional reactions.

Abstract: A new non-pharmacological method of distraction was tested with 57 children during their annual flu vaccination. Given children's growing enthusiasm for technological devices, a humanoid robot was programmed to interact with them while a nurse administered the vaccination. Children smiled more often with the robot, as compared to the control condition, but they did not cry less. Parents indicated that their children held stronger memories for the robot than for the needle, wanted the robot in the future, and felt empowered to cope. We conclude that children and their parents respond positively to a humanoid robot at the bedside.

Beran|Tanya N|TN|
Ramirez-Serrano|Alex|A|
Vanderkooi|Otto G|OG|
Kuhn|Susan|S|

robotics
vaccination
human–robot interaction
immunization
pain management
pediatric


Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats.

Abstract: Tramadol is an opioid used as analgesic for treating moderate or sever pain. The long-term use of tramadol can induce several deleterious effects. We investigated the impact of chronic tramadol administration on the cerebrum of rats, focusing on oxidative damage, inflammation, apoptosis and changes in monoamine neurotransmitters. Rats received 30 or 60 mg/kg body weight tramadol dissolved in physiological saline daily for 8 weeks via oral gavage. Tramadol-induced rats showed significantly increased cerebral lipid peroxidation and nitric oxide, and deceased GSH content and activity and expression of the antioxidant enzymes. Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-α and IL-6) and expression of NF-κB, iNOS, TNF-α and IL-6 in the cerebrum of rats. Monoamine neurotransmitters, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and gene and protein expression levels of p53 and Bax were significantly increased in the cerebrum of tramadol-induced rats. In contrast, chronic tramadol administration down-regulated Bcl-2 both gene and protein expression in the cerebrum of rats. In conclusion, our results indicate that the neurotoxic effect of chronic tramadol consumption is mediated via oxidative stress, inflammation and apoptosis. Tramadol provoked lipid peroxidation, up-regulated inflammation and apoptosis markers and altered neurotransmission in the cerebrum of rats.

Tramadol Inflammation Apoptosis 8-Oxo-dG ROS


Reprint of "versatile and stable vectors for efficient gene expression in Ralstonia eutropha H16".

Abstract: The Gram-negative β-proteobacterium Ralstonia eutropha H16 is primarily known for polyhydroxybutyrate (PHB) production and its ability to grow chemolithoautotrophically by using CO2 and H2 as sole carbon and energy sources. The majority of metabolic engineering and heterologous expression studies conducted so far rely on a small number of suitable expression systems. Particularly the plasmid based expression systems already developed for the use in R. eutropha H16 suffer from high segregational instability and plasmid loss after a short time of fermentation. In order to develop efficient and highly stable plasmid expression vectors for the use in R. eutropha H16, a new plasmid design was created including the RP4 partitioning system, as well as various promoters and origins of replication. The application of minireplicons derived from broad-host-range plasmids RSF1010, pBBR1, RP4 and pSa for the construction of expression vectors and the use of numerous, versatile promoters extend the range of feasible expression levels considerably. In particular, the use of promoters derived from the bacteriophage T5 was described for the first time in this work, characterizing the j5 promoter as the strongest promoter yet to be applied in R. eutropha H16. Moreover, the implementation of the RP4 partition sequence in plasmid design increased plasmid stability significantly and enables fermentations with marginal plasmid loss of recombinant R. eutropha H16 for at least 96h. The utility of the new vector family in R. eutropha H16 is demonstrated by providing expression data with different model proteins and consequently further raises the value of this organism as cell factory for biotechnological applications including protein and metabolite production.

Gruber|Steffen|S| Hagen|Jeremias|J| Schwab|Helmut|H| Koefinger|Petra|P|

D020118:Cupriavidus necator
D018628:Gene Dosage
D015870:Gene Expression
D005822:Genetic Vectors
D060847:Metabolic Engineering
D010957:Plasmids
D011401:Promoter Regions, Genetic

Ralstonia eutropha H16
Expression system
Promoter
Origin of replication
Plasmid stability


Invasive fungi-derived defensins kill drug-resistant bacterial pathogens.

Abstract: Fungi-derived defensins are a class of antimicrobial peptides with therapeutic potential due to their high antibacterial efficacy and low toxicity. Based on the genomic strategy, we have identified 68 fungal defensin-like peptides (fDLPs) in five new genera, including Trichosporon, Apophysomyces, Lichtheimia, Beauveria and Scedosporium and characterized a new synthetic defensin (scedosporisin) from an invasive fungus. It was active against Gram-positive bacteria but not active against negative bacteria. Importantly, it killed several clinical resistant isolates such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci at low molecular concentrations. Scedosporisin showed low hemolysis and cytotoxicity and high serum stability. The killing kinetics of scedosporisin-2 against a clinical isolate of MRSA showed that it killed the bacteria more rapidly than that of vancomycin. Homology modeling analysis show that scedosporisin adopted a typical cysteine stabilized α-helical and β-sheet fold with a local hydrophobic patch. Scedosporisin significantly improved the survival rate of mice in the peritonitis model. This work has greatly expanded the library of fDLPs, and successfully selected leading molecules for antimicrobial drug reserves.

Scedosporium
Vancomycin-resistant Enterococci
Hydrophobicity
Fungi


Thermoplastic wrapped lead sheet to reduce cardiac device cumulative dose.

Abstract: The objective of this project is to evaluate the percentage dose reduction in cardiac implantable electronic devices (CIEDs) using a thermoplastic wrapped lead sheet. The dose to CIED is evaluated in various situations with and without a lead shield. The efficiency of this type of shielding is supported by measurements made with a commercial plastic scintillation detector (PSD). Percentage depth dose (PDD) curve and lateral dose measurements (LDMs) were made with and without shielding for photon and electron beams. Photon LDMs were made at a depth of 0.5 cm. PSD measurements were compared with dose calculation from the treatment planning system (TPS). The benefit of shielding is greater at 23 MV than at 6 MV, with an average reduction of 71% and 59% of dose, respectively, for out-of-field distance range between 3 and 15 cm. Measurement of posterior beams shows there is no significant increase in skin dose due to backscatter from the lead sheet even when the field intercepts it. Large deviations between TPS calculation and measurements have been observed. The use of lead shielding with an anterior field is advised and provides an easy way to decrease the cumulative dose to CIEDs. Interception of shielding by an electron beam would increase significantly the cumulative dose to CIED for high energies or decrease the quality of the treatment. For a posterior out-of-field, shielding does not have a significant impact on CIED dose.

CIED
Shielding
Plastic scintillation detector
Treatment planning system
Out-of-field dose


The Potential of Oxygenation-Sensitive CMR in Heart Failure.

Abstract:
PURPOSE OF REVIEW
Cardiac magnetic resonance imaging (CMR) use in the context of heart failure (HF) has increased over the last decade as it is able to provide detailed, quantitative information on function, morphology, and myocardial tissue composition. Furthermore, oxygenation-sensitive CMR (OS-CMR) has emerged as a CMR imaging method capable of monitoring changes of myocardial oxygenation without the use of exogenous contrast agents.

RECENT FINDINGS
The contributions of OS-CMR to the investigation of patients with HF includes not only a fully quantitative assessment of cardiac morphology, function, and tissue characteristics, but also high-resolution information on both endothelium-dependent and endothelium-independent vascular function as assessed through changes of myocardial oxygenation. In patients with heart failure, OS-CMR can provide deep phenotyping on the status and important associated pathophysiology as a one-stop, needle-free diagnostic imaging test.

Oxygenation-sensitive CMR
CMR
Heart failure
OS-CMR
Myocardial oxygenation
Microvascular dysfunction


Nonspecific arm pain.

Abstract: Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Moradi|Ali|A|
Ebrahimzadeh|Mohammad H|MH|
Ring|David|D|

Nonspecific arm pain
Arm
Idiopathic arm pain
Shoulder


Assessment of the interns' ability based on Dundee model in Shiraz University of Medical Sciences.

Abstract:
INTRODUCTION
The importance of medical profession and the role of the physician in society is no secret to anyone. Skills and competencies in clinical practice are necessary for the medical profession. In fact, in patient care, doctors require practical skills in addition to scientific knowledge. This study examines the potentials of medical school students in three areas of doing the right thing, doing the right thing in an intermediate range, and doing the right thing by the right person.

METHODS
This study was done in a descriptive-analytical and sectional model. The population of this study was all interns of Shiraz University of Medical Sciences who were passing internship at Internal Medicine, Surgery, Pediatrics, Obstetrics and Emergency wards. About 100 persons were selected by simple randomization. In order to collect data, a questionnaire with 12 questions was designed in two parts. The questionnaire was approved by 7 Faculty members of Clinical Medicine and Medical Education, and its reliability was approved by test-retest method on 20 medical students in the form of a pilot study and through Cronbach's alpha (82%). Collected data were analyzed by SPSS software version 14 using descriptive statistical methods.

RESULTS
Results showed that within the inner circle, interns evaluated their skills in surgery, internal medicine, and gynecology wards, intermediate and at other wards as weak. Also within the center circle, interns evaluated adequate educational evidence-based training in the field of medicine, and sufficiency of educational training in the field of clinical decision making and clinical care as suitable.

CONCLUSION
According to the results, it seems that medical interns' skills in performing most medical skills are moderate. So teaching students by new educational methods and workshop techniques, using experienced teachers will be effective. The use of clinical skills training centers and objective assessment methods for the students' skills, especially before entering the clinical departments, is very important.

Amini|Mitra|M|
Abiri|Samaneh|S|
Nabeiei|Parisa|P|
Ghanavati|Shirin|S|
Hayat|Ali Asghar|AA|
Kojuri|Javad|J|


Grey matter differences associated with age and sex hormone levels between premenopausal and perimenopausal women: A voxel-based morphometry study.

Abstract: The present study aimed to explore brain morphological alterations associated with age and sex hormone levels between premenopausal and perimenopausal women using magnetic resonance imaging (MRI) T1 -weighted structural images. Thirty-two premenopausal women aged (mean ± SD) 47.75 ± 1.55 years and twenty-five recently perimenopausal women aged 51.60 ± 1.63 years were evaluated for sex hormone levels, including prolactin, follicle-stimulating hormone, luteinising hormone, oestradiol, free testosterone and progesterone. A 3.0-Tesla MRI scanner was utilised to acquire T1 images. Voxel-based morphometry (VBM) was used to evaluate changes in grey matter volume between the two groups. The general linear model was applied with false discovery rate correction for between group voxel-wise statistics. Spearman partial correlation analyses were conducted between age, sex hormone levels and regions of grey matter volume showing significant differences between the two groups. The VBM analysis revealed that age and menopause per se lead to grey matter volume reduction in certain brain structures. These structural changes might be potential causes of sexual dysfunction, nervous system degeneration and depression, which need to be examined in future studies. Our findings might provide evidence and guide future research in understanding the menopausal transition.

Lu|Weizhao|W|0000-0002-2941-9791 Guo|Wei|W| Hou|Kun|K| Zhao|Huihui|H| Shi|Liting|L| Dong|Kejiang|K| Qiu|Jianfeng|J|

age
sex hormone
voxel-based morphometry
magnetic resonance imaging
menopause transition


Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

Abstract:
BACKGROUND
Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations.

OBJECTIVE
To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache.

DESIGN
Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet.

RESULTS
Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations.

CONCLUSION
Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA.

Taha|Ameer Y|AY|
Cheon|Yewon|Y|
Faurot|Keturah F|KF|
Macintosh|Beth|B|
Majchrzak-Hong|Sharon F|SF|
Mann|J Douglas|JD|
Hibbeln|Joseph R|JR|
Ringel|Amit|A|
Ramsden|Christopher E|CE|

Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs)


Prognostic Value of Tricuspid Valve Geometry and Leaflet Coaptation Status in Patients Undergoing Tricuspid Annuloplasty: A Three-Dimensional Echocardiography Study.

Abstract:
BACKGROUND
The advent of three-dimensional echocardiography (3DE) enables detailed evaluation of the tricuspid valve (TV) apparatus; nonetheless, the clinical value of preoperative 3DE is unknown in patients undergoing tricuspid annuloplasty (TA). The aim of this study was to evaluate the prognostic value of TV geometric parameters and leaflet coaptation status evaluated by 3DE in patients undergoing TA.

METHODS
A total of 122 patients who underwent TA during left-sided heart valve surgery were prospectively evaluated. Detailed 3DE was performed before surgery. Adverse outcome was defined as the occurrence of heart failure requiring hospital admission or all-cause mortality following TA.

RESULTS
A total of 33 adverse events (17 heart failures and 16 deaths) occurred during a median follow-up of 36 months. Tethering volume (hazard ratio = 1.32; 95% CI = 1.05-1.66; P = .01) and ratio of total leaflet length to closure length (hazard ratio = 1.07; 95% CI = 1.03-1.12; P < .01) were associated with adverse events after adjustment for age, sex, and tricuspid regurgitation vena contracta width. Receiver-operator characteristic curve analysis revealed that tethering volume (area under curve = 0.73) and ratio of total leaflet length to closure length (area under curve = 0.75) were most associated with adverse events at 1-year follow-up. The presence of either a large tethering volume or a low ratio of total leaflet length to closure length was predictive of an adverse outcome 1 year following TA.

CONCLUSIONS
Our study suggests that 3DE-derived TV tethering volume and ratio of total leaflet length to closure length are important preoperative measures associated with adverse events in patients undergoing TA.

Chen|Yan|Y|
Liu|Ying-Xian|YX|
Yu|Yu-Juan|YJ|
Wu|Mei-Zhen|MZ|
Lam|Yui-Ming|YM|
Sit|Ko-Yung|KY|
Chan|Daniel Tai-Leung|DT|
Ho|Cally Ka-Lai|CK|
Ho|Lai-Ming|LM|
Fang|Li-Gang|LG|
Zhang|Shu-Yang|SY|
Lau|Chu-Pak|CP|
Au|Wing-Kuk|WK|
Tse|Hung-Fat|HF|
Yiu|Kai-Hang|KH|

Tricuspid valve geometry
Tricuspid annuloplasty
Three-dimensional echocardiography
Tricuspid regurgitation


Understanding the preference for homebirth; an exploration of key barriers to facility delivery in rural Tanzania.

Abstract:
BACKGROUND
There is limited information on the effect of expectant parents' socio-cultural perceptions and practices on the use of skilled birth attendants (SBAs) in rural Tanzania. The purpose of this study was to explore the socio-cultural barriers to health facility birth and SBA among parents choosing home birth in rural Tanzania, specifically in the Rukwa Region.

METHODS
This study used a descriptive exploratory methodology. Purposive sampling was used to recruit study participants for both in-depth interviews (IDIs) and focused group discussions (FGDs). Qualitative research methods, including FGDs and IDIs, were utilized in data collection. The respondents were men and women whose youngest child had been born at home within the prior 12 months. A thematic approach was used for data analysis.

RESULTS
The main themes that emerged regarding barriers to the use of health facility were 1) limited decision-making by men on place of delivery; 2) low risk perception by men and its interference with health facility birth; 3) men's limited resource mobilization for health facility birth and 4) females' perceptions that pregnancy and childbirth are low-risk events.

CONCLUSION
This qualitative study demonstrates that apart from well-documented structural barriers to skilled birth attendance in rural Tanzania, the low risk perception among both men and women plays a substantial role. The low risk perception among both men and women affects the use of SBAs in two ways. First, women become negligent and take risk of delivering at home. Second, male partners do not seriously mobilize resources for health facility childbirth. These findings reinforce the urgent need to implement creative programs to increase genuine male participation in facilitation of health facility childbirth.

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

Rural Tanzania
Health facility
Home childbirth
Place of birth
Pregnancy complication
Sumbawanga


Cathodal Transcranial Direct Current Stimulation (tDCS) Applied to the Left Premotor Cortex Interferes with Explicit Reproduction of a Motor Sequence.

Abstract: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that allows the modulation of cortical excitability. TDCS effects can outlast the stimulation period presumably due to changes of GABA concentration which play a critical role in use-dependent plasticity. Consequently, tDCS and learning-related synaptic plasticity are assumed to share common mechanisms. Motor sequence learning has been related to activation changes within a cortico-subcortical network and findings from a meta-analysis point towards a core network comprising the cerebellum as well as the primary motor (M1) and the dorsolateral premotor cortex (dPMC). The latter has been particularly related to explicit motor learning by means of brain imaging techniques. We here test whether tDCS applied to the left dPMC affects the acquisition and reproduction of an explicitly learned motor sequence. To this end, 18 healthy volunteers received anodal, cathodal and sham tDCS to the left dPMC and were then trained on a serial reaction time task (SRTT) with their right hand. Immediately after the training and after overnight sleep, reproduction of the learned sequence was tested by means of reaction times as well as explicit recall. Regression analyses suggest that following cathodal tDCS reaction times at the end of the SRTT training-block explained a significant proportion of the number of correctly reported sequence items after overnight sleep. The present data suggest the left premotor cortex as one possible target for the application of non-invasive brain stimulation techniques in explicit motor sequence learning with the right hand.

non-invasive brain stimulation
motor sequence learning
SRTT
consolidation


Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina.

Abstract: It is currently believed that aging is closely linked with mitochondrial dysfunction, and that resveratrol exhibits anti-aging and neuroprotective effects by improving mitochondrial function, even though the mechanisms are not well defined. This study explored mitochondrial quality (mitochondrial DNA integrity and copy number), mitochondrial function (fusion/fission, mitophagy/autophagy), antioxidant system and activity of the Akt/mTOR and Ampk/Sirt1/Pgc1α pathways, and inflammation in aging zebrafish retinas to identify the probable mechanisms of resveratrol's anti-aging and neuroprotective effects. mtDNA integrity, mtDNA copy number, mitochondrial fusion regulators, mitophagy, and antioxidant-related genes were all decreased whereas Akt/mTOR activity and inflammation was increased upon aging in zebrafish retinas. Resveratrol was shown to not only increase mitochondrial quality and function, but also to suppress Akt/mTOR activity in zebrafish retinas. These results support the notion that mitochondrial dysfunction and increased Akt/mTOR activity are major players in age-related retinal neuropathy in zebrafish, and demonstrate a trend towards mitochondrial fragmentation in the aging retina. Importantly, resveratrol promoted mitochondrial function, up-regulating Ampk/Sirt1/Pgc1α, and down-regulated Akt/mTOR pathway activity in zebrafish retinas, suggesting that it may be able to prevent age-related oculopathy.

Wang|Ning|N| Luo|Zhiwen|Z| Jin|Ming|M| Sheng|Weiwei|W| Wang|Han-Tsing|HT| Long|Xinyi|X| Wu|Yue|Y| Hu|Piaopiao|P| Xu|Hong|H| Zhang|Xu|X|

mitochondrial dysfunction
resveratrol
retina
mitophagy
mTOR
aging zebrafish


A look into the use of Raman spectroscopy for brain and breast cancer diagnostics: linear and non-linear optics in cancer research as a gateway to tumor cell identity.

Abstract: Introduction: Currently, intensely developing of linear and non-linear optical methods for cancer detection provides a valuable tool to improve sensitivity and specificity. One of the main reasons for insufficient progress in cancer diagnostics is related to the fact that most cancer types are not only heterogeneous in their genetic composition but also reside in varying microenvironments and interact with different cell types. Until now, no technology has been fully proven for effective detecting of invasive cancer, which infiltrating the extracellular matrix.Areas covered: This review investigates the current status of Raman spectroscopy and Raman imaging for brain and breast cancer diagnostics. Moreover, the review provides a comprehensive overview of the applicability of atomic force microscopy (AFM), linear and non-linear optics in cancer research as a gateway to tumor cell identity.Expert commentary: A combination of linear and non-linear optics, particularly Raman-driven methods, has many additional advantages to identify alterations in cancer cells that are crucial for their proliferation and that distinguish them from normal cells.

Abramczyk|Halina|H| Brozek-Pluska|Beata|B| Jarota|Arkadiusz|A| Surmacki|Jakub|J| Imiela|Anna|A| Kopec|Monika|M|

D014408:Biomarkers, Tumor
D001932:Brain Neoplasms
D001943:Breast Neoplasms
D044127:Epigenesis, Genetic
D005260:Female
D006801:Humans
D008297:Male
D025202:Molecular Diagnostic Techniques
D058990:Molecular Targeted Therapy
D013059:Spectrum Analysis, Raman

Cancer diagnostics by using Raman spectroscopy and imaging


Modified Zeolite/Polysulfone Mixed Matrix Membrane for Enhanced CO2/CH4 Separation.

Abstract: In recent years, mixed matrix membranes (MMMs) have received worldwide attention for their potential to offer superior gas permeation and separation performance involving CO2 and CH4. However, fabricating defect-free MMMs still remains as a challenge where the incorporation of fillers into MMMs has usually led to some issues including formation of undesirable interfacial voids, which may jeopardize the gas separation performance of the MMMs. This current work investigated the incorporation of zeolite RHO and silane-modified zeolite RHO (NH2-RHO) into polysulfone (PSf) based MMMs with the primary aim of enhancing the membrane's gas permeation and separation performance. The synthesized zeolite RHO, NH2-RHO, and fabricated membranes were characterized by X-ray diffraction (XRD) analysis, Fourier transform infrared-attenuated total reflection (FTIR-ATR), thermogravimetric analysis (TGA) and field emission scanning election microscopy (FESEM). The effects of zeolite loading in the MMMs on the CO2/CH4 separation performance were investigated. By incorporating 1 wt% of zeolite RHO into the MMMs, the CO2 permeability and ideal CO2/CH4 selectivity slightly increased by 4.2% and 2.7%, respectively, compared to that of a pristine PSf membrane. On the other hand, a significant enhancement of 45% in ideal CO2/CH4 selectivity was attained by MMMs incorporated with 2 wt% of zeolite NH2-RHO compared to a pristine PSf membrane. Besides, all MMMs incorporated with zeolite NH2-RHO displayed higher ideal CO2/CH4 selectivity than that of the MMMs incorporated with zeolite RHO. By incorporating 1-3 wt% zeolite NH2-RHO into PSf matrix, MMMs without interfacial voids were successfully fabricated. Consequently, significant enhancement in ideal CO2/CH4 selectivity was enabled by the incorporation of zeolite NH2-RHO into MMMs.

polysulfone
mixed matrix membranes (MMMs)
zeolite RHO
CO2 separation
silane modification


Olfactory function in mild cognitive impairment and Alzheimer's disease: A meta-analysis.

Abstract:
OBJECTIVE
Olfactory function is altered in mild cognitive impairment (MCI) and Alzheimer's disease (AD); therefore, it may serve as a useful tool for the early detection of MCI before its advancement to AD. The aim of this meta-analysis was to investigate olfactory deficits in patients with MCI and AD.

STUDY DESIGN
Literature search.

METHODS
A search was conducted of the electronic databases PubMed, Embase, and Web of Science from their inception until 2017. We included original articles with adequate data on the identification, threshold, and/or discrimination of olfactory function in MCI or AD. The standard mean difference and 95% confidence interval (CI) were calculated. The studies were weighted according to inverse variance estimates. The effect sizes were categorized as small [Cohen's d = 0.2], medium (d = 0.5), or large (d ≥ 0.8) based on these methods. Subgroup analyses were performed based on mean age and sex differences between the groups.

RESULTS
Twelve articles (reporting 21 effects) examining 563 patients with MCI and 788 patients with AD, were included in the meta-analysis. Compared to MCI, AD had moderate to large heterogeneous effects on olfactory function (Cohen's d = 0.64, 95% CI: 0.50, 0.78). Olfactory identification tests demonstrated larger effects (d = 0.71, 95% CI: 0.51, 0.91) than did tests of other olfactory domains.

CONCLUSIONS
Meta-analysis results revealed that olfactory identification was more profoundly impaired in patients with AD than in those with MCI. These findings suggest that a simple test of odor identification is valuable in differentiating individuals at a risk of AD.

LEVEL OF EVIDENCE
NA Laryngoscope, 129:362-369, 2019.

Mild cognitive impairment
Alzheimer's disease
meta-analysis
dementia
olfaction


The effect of aging and cardiorespiratory fitness on the lung diffusing capacity response to exercise in healthy humans.

Abstract: Aging is associated with deterioration in the structure and function of the pulmonary circulation. We characterized the lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary-capillary blood volume (Vc) response to discontinuous incremental exercise at 25, 50, 75, and 90% of peak work (Wpeak) in four groups: 1) Young [27 ± 3 yr, maximal oxygen consumption (V̇o2max): 110 ± 18% age predicted]; 2) Young Highly Fit (27 ± 3 yr, V̇o2max: 147 ± 8% age predicted); 3) Old (69 ± 5 yr, V̇o2max: 116 ± 13% age predicted); and 4) Old Highly Fit (65 ± 5 yr, V̇o2max: 162 ± 18% age predicted). At rest and at 90% Wpeak, DLCO, DmCO, and Vc were decreased with age. At 90% Wpeak, DLCO, DmCO, and Vc were greater in Old Highly Fit vs. Old adults. The slope of the DLCO-cardiac output (Q̇) relationship from rest to end exercise at 90% Wpeak was not different between Young, Young Highly Fit, Old, and Old Highly Fit (1.35 vs. 1.44 vs. 1.10 vs. 1.35 mlCO·mmHg-1·liter blood-1, P = 0.388), with no evidence of a plateau in this relationship during exercise; this was also true for DmCO-Q̇ and Vc-Q̇. V̇o2max was positively correlated with 1) DLCO, DmCO, and Vc at rest; and 2) the rest to end exercise change in DLCO, DmCO, and Vc. In conclusion, these data suggest that despite the age-associated deterioration in the structure and function of the pulmonary circulation, expansion of the pulmonary capillary network does not become limited during exercise in healthy individuals regardless of age or cardiorespiratory fitness level.NEW & NOTEWORTHY Healthy aging is a crucial area of research. This article details how differences in age and cardiorespiratory fitness level affect lung diffusing capacity, particularly during high-intensity exercise. We conclude that highly fit older adults do not experience a limit in lung diffusing capacity during high-intensity exercise. Interestingly, however, we found that highly fit older individuals demonstrate greater values of lung diffusing capacity during high-intensity exercise than their less fit age-matched counterparts.

Coffman|Kirsten E|KE|
Carlson|Alex R|AR|
Miller|Andrew D|AD|
Johnson|Bruce D|BD|
Taylor|Bryan J|BJ|

lung diffusing capacity
pulmonary circulation
alveolar-capillary membrane conductance
pulmonary-capillary blood volume
maximal aerobic capacity


Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections.

Abstract: Polymeric nanocarriers (PNs) have demonstrated to be a promising alternative to treat intracellular infections. They have outstanding performance in delivering antimicrobials intracellularly to reach an adequate dose level and improve their therapeutic efficacy. PNs offer opportunities for preventing unwanted drug interactions and degradation before reaching the target cell of tissue and thus decreasing the development of resistance in microorganisms. The use of PNs has the potential to reduce the dose and adverse side effects, providing better efficiency and effectiveness of therapeutic regimens, especially in drugs having high toxicity, low solubility in the physiological environment and low bioavailability. This review provides an overview of nanoparticles made of different polymeric precursors and the main methodologies to nanofabricate platforms of tuned physicochemical and morphological properties and surface chemistry for controlled release of antimicrobials in the target. It highlights the versatility of these nanosystems and their challenges and opportunities to deliver antimicrobial drugs to treat intracellular infections and mentions nanotoxicology aspects and future outlooks.

drugs
intracellular infections
polymeric nanocarriers
nanotoxicology
administration route
biodistribution
pharmacokinetics
polymeric properties