Managing surgical wound care: review of Leukomed Control dressings.

Abstract: Optimal management of surgical wounds is an important part of postoperative recovery. The aim of postoperative wound care is to facilitate rapid wound closure, while preventing complications and promoting minimal disturbance, to achieve the best functional and aesthetic results. Health professionals should seek to optimise the process of acute wound healing, observe progress, and prevent wound complications. Dressings that permit extended wear time, and are transparent and so allow early recognition without the need for unnecessary changes, have the potential to minimise the effect on patients and the wider health economy. This article reviews recommendations for surgical wound care, and introduces the recently launched Leukomed Control dressing that is entirely transparent and allows greater flexibility, breathability, and visualisation of the wound.

Dressings
Wound healing
Cost-effectiveness
Quality of life
Surgical wound infection


Open-wedge high tibial osteotomy for spontaneous osteonecrosis of the medial tibial plateau shows excellent clinical outcomes.

Abstract: PurposeThere have been few reports on medial tibial plateau osteonecrosis, and treatment options remain controversial. This study aimed to evaluate the clinical outcomes of open-wedge high tibial osteotomy (OWHTO) for osteonecrosis of the medal tibial plateau.MethodsPatients who underwent OWHTO for spontaneous osteonecrosis of the medial tibial plateau from November 2013 to September 2017 at our institution and followed up for at least 2 years after surgery were included in this study. Patients with history of alcohol abuse and corticosteroid therapy were excluded. Clinical evaluations, including the Japanese Orthopedic Association (JOA) score and the Oxford Knee Score (OKS), were measured preoperatively and at the final followup. Radiological evaluations included the weight-bearing line ratio (WBLR) and the lesion stage of the osteonecrosis according to Carpintero, Lotke, and the modified Ficat and Arlet classification. The area and size of the necrosis and the type of meniscus tear were also evaluated using preoperative magnetic resonance imaging (MRI). Additionally, cartilage regeneration was evaluated at plate removal.ResultsTwelve cases that underwent OWHTO for spontaneous osteonecrosis of the medial tibial plateau were enrolled. Eleven cases had isolated medial tibial osteonecrosis, and one case had both femoral and tibial osteonecrosis. The mean age was 59.6 ± 9.0 years, and the mean follow-up period was 41.8 ± 17.6 months.The WBLR significantly changed after OWHTO (24.0% ± 10.7% to 66.3% ± 6.7%, P < 0.001), and all clinical scores significantly improved after surgery: JOA score 63.3 ±12.3 to 95.0 ± 4.8, OKS 27.4 ± 7.8 to 42.6 ± 4.1, both 0.001. There were no adverse complications requiring additional surgery. The MRI findings revealed that all cases had meniscal lesions in addition to a necrotic lesion. Second-look arthroscopy was performed at plate removal in 11 cases, and cartilage regeneration was observed in 9/11 cases (81.8%).ConclusionsThis study's results demonstrated that OWHTO is an effective procedure for spontaneous osteonecrosis of the medial tibial plateau with respect to subjective and objective clinical outcomes.

Goshima|Kenichi|K| Sawaguchi|Takeshi|T| Shigemoto|Kenji|K| Iwai|Shintaro|S| Fujita|Kenji|K| Yamamuro|Yuki|Y|

Open-wedge high tibial osteotomy
osteonecrosis
medial tibial plateau


Fatal Rhabdomyolysis in a COVID-19 Patient on Rosuvastatin.

Abstract: It is well-established by now that COVID-19 can have a wide variety of neuromuscular manifestations, including rhabdomyolysis. Weakness and elevated creatinine kinase (CK) have been documented as the initial presentation of COVID-19. Myopathy from statin use has also been well-established since the introduction of this class of medication, and the common pathologic mechanism of both entities may have been mitochondrial dysfunction. We present here the case of a COVID-19 patient on rosuvastatin who developed rhabdomyolysis with CK above 1,000,000 units/L. The patient did not present with any respiratory difficulty and responded poorly to treatment, resulting in his untimely demise. COVID-19 may have accentuated an otherwise survivable condition by means of extra stress on mitochondrial homeostasis. Understanding the actual mechanism will be important in the development and utilization of medications in the fight against COVID-19.

Anklesaria|Zafia|Z|
Frankman|Jonathan|J|
Gordin|Jonathan|J|
Zhan|Jennifer|J|
Liu|Antonio K|AK|


In-Situ Measurements in Microscale Gas Flows-Conventional Sensors or Something Else?

Abstract: Within the last few decades miniaturization has a driving force in almost all areas of technology, leading to a tremendous intensification of systems and processes. Information technology provides now data density several orders of magnitude higher than a few years ago, and the smartphone technology includes, as well the simple ability to communicate with others, features like internet, video and music streaming, but also implementation of the global positioning system, environment sensors or measurement systems for individual health. So-called wearables are everywhere, from the physio-parameter sensing wrist smart watch up to the measurement of heart rates by underwear. This trend holds also for gas flow applications, where complex flow arrangements and measurement systems formerly designed for a macro scale have been transferred into miniaturized versions. Thus, those systems took advantage of the increased surface to volume ratio as well as of the improved heat and mass transfer behavior of miniaturized equipment. In accordance, disadvantages like gas flow mal-distribution on parallelized mini- or micro tubes or channels as well as increased pressure losses due to the minimized hydraulic diameters and an increased roughness-to-dimension ratio have to be taken into account. Furthermore, major problems are arising for measurement and control to be implemented for in-situ and/or in-operando measurements. Currently, correlated measurements are widely discussed to obtain a more comprehensive view to a process by using a broad variety of measurement techniques complementing each other. Techniques for correlated measurements may include commonly used techniques like thermocouples or pressure sensors as well as more complex systems like gas chromatography, mass spectrometry, infrared or ultraviolet spectroscopy and many others. Some of these techniques can be miniaturized, some of them cannot yet. Those should, nevertheless, be able to conduct measurements at the same location and the same time, preferably in-situ and in-operando. Therefore, combinations of measurement instruments might be necessary, which will provide complementary techniques for accessing local process information. A recently more intensively discussed additional possibility is the application of nuclear magnetic resonance (NMR) systems, which might be useful in combination with other, more conventional measurement techniques. NMR is currently undergoing a tremendous change from large-scale to benchtop measurement systems, and it will most likely be further miniaturized. NMR allows a multitude of different measurements, which are normally covered by several instruments. Additionally, NMR can be combined very well with other measurement equipment to perform correlative in-situ and in-operando measurements. Such combinations of several instruments would allow us to retrieve an "information cloud" of a process. This paper will present a view of some common measurement techniques and the difficulties of applying them on one hand in a miniaturized scale, and on the other hand in a correlative mode. Basic suggestions to achieve the above-mentioned objective by a combination of different methods including NMR will be given.

miniaturization
measurement and control
advanced measurement technologies
gas flows in micro scale
integrated micro sensors


Extraintestinal pathogenic Escherichia coli (ExPEC) of human and avian origin belonging to sequence type complex 95 (STC95) portray indistinguishable virulence features.

Abstract: Extraintestinal pathogenic Escherichia coli (ExPEC) strains of certain genetic lineages are frequently implicated in a wide range of diseases in humans and birds. ExPEC strains belonging to the phylogenetic lineage/sequence type complex 95 (STC95) are one such prominent lineage that is commonly isolated from extraintestinal infections such as systemic disease in poultry and urinary tract infections (UTIs), neonatal meningitis and sepsis in humans. Several epidemiological studies have indicated that ST95 strains obtained from such infections may share similar virulence genes and other genomic features. However, data on their ability to establish infections in vivo as deduced from the manifestation of similar virulence phenotypes remain elusive. In the present study, 116 STC95 ExPEC isolates comprising 55 human and 61 avian strains, possessing similar virulence gene patterns, were characterized in vitro using adhesion, invasion, biofilm formation and serum bactericidal assays. Overall, STC95 strains from both groups, namely human and birds, were equally capable of adhering to and invading the two mammalian kidney cell lines. Similarly, these strains were able to form strong biofilms in M63 medium. Furthermore, they were equally resistant to the bactericidal activity of human and avian serum. Our cumulative data reinforce the understanding that ST95 strains from poultry present a potential zoonotic risk and therefore need a One Health strategy for a successfull intervention.

Nandanwar|Nishant|N|
Janssen|Traute|T|
Kühl|Michael|M|
Ahmed|Niyaz|N|
Ewers|Christa|C|
Wieler|Lothar H|LH|

Human
Avian
STC95
One Health
Extraintestinal pathogenic E. coli


May-Thurner syndrome presenting as pelvic congestion syndrome and vulvar varicosities in a nonpregnant adolescent.

Abstract: May-Thurner syndrome (MTS) refers to compression of the left common iliac vein (CIV) by the common iliac artery. Although this is typically manifested as acute left lower extremity deep venous thrombosis, MTS is a rare cause of pelvic congestion syndrome. A 17-year-old girl presented with a 5-year history of worsening painful vulvar and labial varicosities. Venography demonstrated pelvic collateralization and left CIV stenosis consistent with MTS. The left CIV was stented with complete radiographic resolution. At 1-year follow-up, the patient is asymptomatic with a widely patent stent. This case highlights the role of endovascular therapy for patients presenting with MTS causing pelvic congestion syndrome.

Khan|Tabassum A|TA|
Rudolph|Karen P|KP|
Huber|Thomas S|TS|
Fatima|Javairiah|J|

May-Thurner syndrome
Pelvic congestion
Intravascular ultrasound


Pulmonary infections following immunosuppressive treatments during hospitalization worsen the short-term vital prognosis for patients with connective tissue disease-associated interstitial pneumonia.

Abstract:
OBJECTIVE
Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP.

METHODS
A multicenter, retrospective study was conducted that collected data from patients with CTD who had been hospitalized for commencing or intensifying immunosuppressive treatment of CTD-IP using a standardized case report form. Risk factors were identified using the Cox proportional hazard regression model.

RESULTS
A total of 322 CTD-IP patients were enrolled with rheumatoid arthritis (n = 84), systemic lupus erythematosus (n = 13), polymyositis (n = 33), dermatomyositis (n = 69), systemic sclerosis (n = 55), mixed connective tissue disease (n = 21), microscopic polyangiitis (n = 19), and overlap syndrome (n = 28). Of the 42 patients who died during hospitalization, 22 died from CTD-IP, 15 from CTD-IP and pulmonary infection, 2 from pulmonary infection, and 3 from other causes. Age ≥ 65 years and development of pulmonary infections after commencing or intensifying immunosuppressive treatments were identified as risk factors for death during hospitalization after adjusting for covariates.

CONCLUSION
Careful consideration of the benefit-risk balance of immunosuppressive treatment for CTD-IP is indispensable for improving the short-term vital prognosis of these patients.

Tanaka|Michi|M| Koike|Ryuji|R| Sakai|Ryoko|R| Saito|Kazuyoshi|K| Hirata|Shintaro|S| Nagasawa|Hayato|H| Kameda|Hideto|H| Hara|Masako|M| Kawaguchi|Yasushi|Y| Tohma|Shigeto|S| Takasaki|Yoshinari|Y| Dohi|Makoto|M| Nishioka|Yasuhiko|Y| Yasuda|Shinsuke|S| Miyazaki|Yasunari|Y| Kaneko|Yuko|Y| Nanki|Toshihiro|T| Watanabe|Kaori|K| Yamazaki|Hayato|H| Miyasaka|Nobuyuki|N| Harigai|Masayoshi|M|

Pulmonary infections
Immunosuppressive treatments
Vital prognosis
Interstitial
pneumonia
Connective tissue disease


Healthy yogurt fortified with n-3 fatty acids from vegetable sources.

Abstract: The concentration of n-3 polyunsaturated fatty acids (PUFA) in yogurt was increased using 5 different vegetable oils obtained from flaxseed, Camelina sativa, raspberry, blackcurrant, and Echium plantagineum. The vegetable oils were added to partially skim milk before lactic fermentation at a concentration adequate enough to cover at least 10% of the recommended daily intake of 2 g/d of α-linolenic acid according to EC regulation no. 432/2012. Microbiological (lactobacilli and streptococci, yeast, and molds), chemical (pH, syneresis, proximate composition, fatty acids, oxidation stability), and sensory evaluations were assessed for all of the fortified yogurts after 0, 7, 14, and 21 d of storage at 4°C. Sensory evaluations were conducted at 21 d of storage at 4°C. Among the yogurts produced, those that were supplemented with flaxseed and blackcurrant oils exhibited the highest α-linolenic acid content (more than 200mg/100 g of yogurt) at the end of storage. The addition of oil did not influence the growth of lactic acid bacteria that were higher than 10(7) cfu/g at 21 d of storage. All of the yogurts were accepted by consumers, except for those supplemented with raspberry and E. plantagineum oils due to the presence of off flavors.

Dal Bello|B|B|
Torri|L|L|
Piochi|M|M|
Zeppa|G|G|

yogurt
vegetable oil
consumer acceptability
healthy benefit
n-3 α-linolenic acid


A Combination of Histological, Physiological, and Proteomic Approaches Shed Light on Seed Desiccation Tolerance of the Basal Angiosperm Amborella trichopoda.

Abstract: Desiccation tolerance allows plant seeds to remain viable in a dry state for years and even centuries. To reveal potential evolutionary processes of this trait, we have conducted a shotgun proteomic analysis of isolated embryo and endosperm from mature seeds of Amborella trichopoda, an understory shrub endemic to New Caledonia that is considered to be the basal extant angiosperm. The present analysis led to the characterization of 415 and 69 proteins from the isolated embryo and endosperm tissues, respectively. The role of these proteins is discussed in terms of protein evolution and physiological properties of the rudimentary, underdeveloped, Amborella embryos, notably considering that the acquisition of desiccation tolerance corresponds to the final developmental stage of mature seeds possessing large embryos.

Villegente|Matthieu|M| Marmey|Philippe|P| Job|Claudette|C| Galland|Marc|M| Cueff|Gwendal|G| Godin|Béatrice|B| Rajjou|Loïc|L| Balliau|Thierry|T| Zivy|Michel|M| Fogliani|Bruno|B| Sarramegna-Burtet|Valérie|V| Job|Dominique|D|

proteomics
seeds
desiccation tolerance
basal angiosperms
Amborella trichopoda


Automated Breast Density Measurements From Chest Computed Tomography Scans.

Abstract: To develop an automated method for quantifying percent breast density from chest computed tomography (CT) scans. A naïve Bayesian classifier based on gray-level intensities and spatial relationships was developed on CT scans from 10 patients diagnosed with Hodgkin lymphoma (HL) and imaged as part of routine clinical care. The algorithm was validated on CT scans from 75 additional HL patients. The classifier was developed and validated using a reference dataset with consensus manual segmentation of fibroglandular tissue. Accuracy was evaluated at the pixel-level to examine how well the algorithm identified pixels with fibroglandular tissue using true and false positive fractions (TPF and FPF, respectively). Quantitative estimates of the patient-level CT percent density were contrasted to each other using the concordance correlation coefficient, ρc, and to subjective ACR BI-RADS density assessments using Kendall's τb. The pixel-level TPF for identifying pixels with fibroglandular tissue was 82.7% (interquartile range of patient-specific TPFs 65.5%-89.6%). The pixel-level FPF was 9.2% (interquartile range of patient-specific FPFs 2.5%-45.3%). Patient-level agreement of the algorithm's automated density estimate with that obtained from the reference dataset was high, ρc = 0.93 (95% CI 0.90-0.96) as was agreement with a radiologist's subjective ACR-BI-RADS assessments, τb = 0.77. It is possible to obtain automated measurements of percent density from clinical CT scans.

Qureshi|Touseef A|TA|
Veeraraghavan|Harini|H|
Sung|Janice S|JS|
Kaplan|Jennifer B|JB|
Flynn|Jessica|J|
Tonorezos|Emily S|ES|
Wolden|Suzanne L|SL|
Morris|Elizabeth A|EA|
Oeffinger|Kevin C|KC|
Pike|Malcolm C|MC|
Moskowitz|Chaya S|CS|

Breast density
Algorithm
Bayes theorem
Risk


Quantifying Dry Milling in Pharmaceutical Processing: A Review on Experimental and Modeling Approaches.

Abstract: Particle size reduction by mechanical means is an important unit operation in the pharmaceutical industry, used to improve flow, solubility, and in amorphization of drugs. It is usually achieved by the fracturing of particles under the action of applied energy. Despite being pervasive in the pharmaceutical field, it is one of the least understood processes owing to the complexity of material and process variables involved during milling. To comprehend the process, efforts should be focused on techniques that measure the particle size as well as the control the process. With the ongoing initiative of US FDA to encourage design in quality, the review is focused on some process analytical tools to characterize particle size distribution as well as process modeling tools to simulate particle size reduction. Additionally, an overview of some fundamental aspects related to milling is provided. To this end, the review is limited, mainly concentrating on some of experimental and modeling approaches used to quantify and understand the physics behind the process of dry milling.

D055598:Chemical Phenomena
D003198:Computer Simulation
D004339:Drug Compounding
D055595:Mechanical Phenomena
D008956:Models, Chemical
D010316:Particle Size
D011208:Powders
D011786:Quality Control
D012995:Solubility

milling
particle size
fracture
process modeling
PAT
mathematical model
mechanical properties
powder technology


Standardized Rat Model Testing Effects of Inflammation and Grafting on Extraction Healing.

Abstract:
BACKGROUND
Loss of alveolar ridge width and height after tooth extraction is well documented, but models to evaluate ridge preservation are neither standardized nor cost-effective. This rat model characterizes the pattern of bone turnover and inflammation after extraction and bone grafting with or without local simvastatin (SIM).

METHODS
Fifty retired-breeder rats underwent extraction of the maxillary right first molar and standard surgical defect creation under inhalation/local anesthesia. The left side of each animal served as unmanipulated control. Untreated groups (n = 8 to 9 per group) were compared (analysis of variance, t test) at days 0, 7, 14, and 28 for alveolar ridge height and width and for markers of inflammation and bone turnover by microcomputed tomography, histology, and enzyme-linked immunosorbent assay. Seventeen additional specimens had defects grafted with either bone mineralized matrix (BMM) or a BMM+SIM conjugate.

RESULTS
Extraction-induced bone loss (BL) was noted on buccal, palatal, and interproximal height (P <0.05) and ridge width (P <0.01). Week 1 inflammation positively correlated with ridge height; thereafter, a more intense inflammatory reaction corresponded to reduction in alveolar bone height and density (r = 0.74; P <0.05; Spearman). BMM+SIM preserved the most interproximal bone height (P <0.01), increased ridge width and bone density (P <0.01), enhanced 7-day prostaglandin E2 (P <0.01), and reduced 28-day inflammation density (P <0.05).

CONCLUSIONS
The standard defect used in the current study paralleled human postextraction alveolar BL. Defect grafting, especially BMM+SIM, reduced inflammation and preserved bone.

Willett|Emily S|ES|
Liu|Jingpeng|J|
Berke|Molly|M|
Giannini|Peter J|PJ|
Schmid|Marian|M|
Jia|Zhenshan|Z|
Wang|Xiaobei|X|
Wang|Xiaoyan|X|
Samson|Kaeli|K|
Yu|Fang|F|
Wang|Dong|D|
Nawshad|Ali|A|
Reinhardt|Richard A|RA|

rats
inflammation
tooth extraction
Bone remodeling


The effect of lead from sediment bioturbation by Lumbriculus variegatus on Daphnia magna in the water column.

Abstract: The present study investigated the bioavailability and potential toxicity to Daphnia magna of lead released to the water column due to bioturbation by Lumbriculus variegatus. Experiments used microcosms with Pb-spiked sediment, with or without worms in the sediment, and with D. magna present in the water column. The daphniids were allowed free movement or were restricted to flow-through containers, in order to assess the influence of their direct contact with the contaminated sediment. A control group consisted of D. magna in clean moderately hard reconstituted water. At the end of the 12-day experiment, D. magna survival, reproduction, biomass, and Pb-bioaccumulation were determined. Water column turbidity and Pb levels were quantified to assess their influence on the Pb toxicity and bioaccumulation. The bioturbation by L. variegatus increased Pb levels and turbidity in the water column. While this resulted in an increased Pb bioaccumulation by the D. magna, the water column Pb levels and the Pb bioaccumulation were insufficient to bring about toxic effects for the survival, reproduction, and biomass of the daphniids. Contact of D. magna with the sediment resulted in an increase in their Pb bioaccumulation, with water turbidity and Pb data, suggesting that these crustaceans also acted as bioturbators. The increase in Pb bioaccumulation in D. magna as a consequence of bioturbation by L. variegatus demonstrates the potential for bioturbation to enhance contaminant toxicity to organisms in the water column, though this potential appeared relatively low in the case of lead.

Blankson|Emmanuel R|ER|
Klerks|Paul L|PL|

Lead
Bioturbation
Lumbriculus variegatus
Daphnia magna
Bioaccumulation


Levels and Distributions of 210Pb and 210Po in Selected Seafood Samples in China and Assessment of Related Dose to Population.

Abstract: In this study, the activity concentrations levels of 210Pb and 210Po in the edible portions of eight seafood samples collected from the Fujian coast of China were determined. The activity concentrations ranged from 0.74 ± 0.08 to 12.6 ± 1.0 Bq/kg for 210Po and from the minimum detectable limit (MDL, 0.80 Bq/kg) to 11. 7 ± 1.1 Bq/kg for 210Pb. The 210Po activity concentration in all the fish organs ranged from 0.68 to 204 Bq/kg (w.w.), and the 210Po activity was mainly concentrated in the stomach, spleen, heart, liver, gonad, and intestine samples. The 210Pb activity concentration in all the fish organs ranged from the MDL to 15.2 Bq/kg (w.w.), and the 210Pb activity was concentrated in the head, fish scale, and gill samples. The annual effective ingestion doses ranged from 82.8 to 255 μSv/a for all age groups, and the lifetime risk of cancers were estimated. Both the effective ingestion doses and cancer risk to humans were within the acceptable ranges.

Kong|Xiangyin|X| Qian|Yuxin|Y| Zheng|Qishan|Q| Ji|Yanqin|Y|

210Pb
210Po
seafoods
dose
activity concentration
radiological risk


Surgical outcomes and complications of sutureless needle-guided intrascleral intraocular lens fixation combined with vitrectomy.

Abstract:
Purpose
: To analyze the surgical outcomes and complications of sutureless needle-guided intrascleral intraocular lens (IOL) implantation (Yamane technique) combined with pars plana vitrectomy.

Methods
Retrospective study of 47 eyes of 46 patients that underwent scleral fixation of IOL by the Yamane technique combined with 3-port pars plana vitrectomy. Demographic data, primary indications for surgery, history of trauma, best corrected visual acuity (BCVA), intraocular pressure (IOP), duration of follow-up, and complications were analyzed.

Results
Mean preoperative BCVA was 0.79 logMAR, which improved to 0.39 logMAR at mean 4.21 months (SD: 4.87 D) follow-up. Mean spherical equivalent pre and postoperative was + 7.64 D (SD: 7.74 D) and - 0.47 D (SD: 2.26 D), respectively. Early postoperative complications included hypotony with cyclodialysis cleft (n = 1; 2%), mild vitreous hemorrhage (n = 2; 4%), raised IOP (n = 2; 4%), and transient corneal edema (n = 2; 4%). Late complications included iris optic capture (n = 1; 2%), retinal detachment (n = 1; 2%), cystoid macular edema (CME; n = 2; 4%), IOL decentration (n = 1; 2%), and decentration and tilting of IOL (n = 1; 2%). Management of complications included laser treatment to cyclodialysis cleft, observation for vitreous hemorrhage, topical and oral IOP lowering agents for raised IOP. CME was managed with topical non-steroidal anti-inflammatory drugs. One eye was subjected IOL refixation. The mean number of surgeries per eye was 1.04.

Conclusion
Combining needle-guided intrascleral IOL implantation with vitrectomy allows management of other posterior segment complications in the same sitting while obviating the need for the second surgery. It provides satisfactory outcomes that are comparable to published studies. However, a longer follow-up will allow a better understanding of the potential advantages of this approach.

complications
intraocular lens
vitrectomy
eye
surgery
trauma
Aphakia
cataract
scleral-fixated IOL


Imbalance of Steroid Hormones in Hamsters Infected with Schistosoma mansoni.

Abstract:
OBJECTIVE
Schistosomiasis is a debilitating disease that affects 200 million people worldwide. Schistosoma haematobium and Schistosoma mansoni are the major causative agents of this disease. Cancer-association and infertility-association in Schistosoma haematobium infection have already been described and it is known that the parasite produces a catechol-estrogen molecule that induces a hormonal imbalance in the host.

METHODS
In order to better understand the relation of hormonal imbalance in experimental Schistosoma mansoni infection, we investigated a serum panel of steroid hormones in Schistosoma mansoni infected hamsters.

RESULTS
We found a decrease in the serum levels of Estradiol (E2), Testosterone and Progesterone in infected females and an increase of Testosterone and a decrease in Progesterone in infected males in comparison with controls.

CONCLUSION
These results indicate that S. mansoni alters the levels of steroid hormones in infected males and females and it will increase the repertoire of data about the host-parasite molecular interplay and its relation with the endocrine system.

Oliveira|Katia C|KC|
Cardoso|Rita|R|
Dos Santos|Antonio C|AC|
Fernandes|Ruben|R|
Botelho|Monica C|MC|

Steroid hormones
Schistosoma mansoni infection
estradiol
progesterone
host-parasite interaction
infertility
testosterone.


Retrograde dissection of the ascending aorta during diagnostic coronary angiography in a patient who previously had resection of the aortic adventitia tumor and coronary bypass grafting.

Abstract: Retrograde dissection of ascending aorta is a very rare but life threating complication of coronary catheterization. Despite the seriousness of the complication, there is little data on the subject. Majority of case reports in literature includes patients without comorbidities that may affect the management. We experienced the retrograde dissection of the ascending aorta in a patient who previously had resection of the tumor originating from aortic root and coronary bypass grafting. No similar case has been reported in literature. The data from literature does not include the patients with comorbidities like previous coronary bypass grafting. For that reason we had hesitation in decision making. Wherefore, the aim of this article is to share our experience in this matter.

Olędzki|Szymon|S| Czechowska|Małgorzata|M| Chlasta|Jacek|J| Gorący|Jarosław|J|

dissection
coronary angiography
complication
sinus of Valsalva


Management of Takayasu arteritis: a systematic review.

Abstract: Assessment of the pattern and extent of arterial involvement and measurement of current disease activity are essential for the management of Takayasu arteritis (TA). Since there is no completed, placebo-controlled, randomized clinical trial, the level of evidence for management of TA is low, generally reflecting the results of open studies, case series and expert opinion. The most commonly used agents include corticosteroids and conventional immunosuppressive agents such as MTX, AZA, MMF and LEF. In patients who remain resistant and/or intolerant to these agents, biologic drugs including TNF inhibitors, rituximab and tocilizumab seem to be promising. Antiplatelet treatment may also lower the frequency of ischaemic events in TA. In the presence of short-segment, critical arterial stenosis, balloon angioplasty or stent graft replacement may be useful. On the other hand, long-segment stenosis with extensive periarterial fibrosis or occlusion requires surgical bypass of the affected segment, which is clearly associated with superior results compared with endovascular intervention. As a general rule, both endovascular intervention and surgical procedures should be avoided during the active phase of the disease. Earlier diagnosis, better assessment of disease activity and future clinical trials will obviously improve the management of TA.

D000305:Adrenal Cortex Hormones
D001688:Biological Products
D003251:Constriction, Pathologic
D019468:Disease Management
D057510:Endovascular Procedures
D006801:Humans
D007166:Immunosuppressive Agents
D010975:Platelet Aggregation Inhibitors
D012720:Severity of Illness Index
D013625:Takayasu Arteritis

management
Takayasu arteritis
Takayasu vasculitis
large vessel vasculitis


Reactivity of cationic agostic and carbene structures derived from platinum(II) metallacycles.

Abstract: This paper describes the formation of new platinacyclic complexes derived from the phosphine ligands PiPr2 Xyl, PMeXyl2 , and PMe2 Ar Xyl 2 (Xyl=2,6-Me2 C6 H3 and Ar Xyl 2=2,6-(2,6-Me2 C6 H3 )2 -C6 H3 ) as well as reactivity studies of the trans-[Pt(C^P)2 ] bis-metallacyclic complex 1 a derived from PiPr2 Xyl. Protonation of compound 1 a with [H(OEt2 )2 ][BArF ] (BArF =B[3,5-(CF3 )2 C6 H3 ]4 ) forms a cationic δ-agostic structure 4 a, whereas α-hydride abstraction employing [Ph3 C][PF6 ] produces a cationic platinum carbene trans-[Pt{PiPr2 (2,6-CH(Me)C6 H3 }{PiPr2 (2,6-CH2 (Me)C6 H3 }][PF6 ] (8). Compounds 4 a and 8 react with H2 to yield the same 1:3 equilibrium mixture of 4 a and trans-[PtH(PiPr2 Xyl)2 ][BArF ] (6), in which one of the phosphine ligands participates in a δ-agostic interaction. DFT calculations reveal that H2 activation by 8 occurs at the highly electrophilic alkylidene terminus with no participation of the metal. The two compounds 4 a and 8 experience C-C coupling reactions of a different nature. Thus, 4 a gives rise to complex trans-[PtH{(E)-1,2-bis(2-(PiPr2 )-3-MeC6 H3 )CHCH}] (7) that contains a tridentate diphosphine-alkene ligand, through agostic CH oxidative cleavage and C-C reductive coupling steps, whereas the C-C coupling reaction in 8 involves classical migratory insertion of its [PtCH] and [PtCH2 ] bonds promoted by platinum coordination of CO or CNXyl. The mechanisms of the CC bond-forming reactions have also been investigated by computational methods.

Campos|Jesús|J| Ortega-Moreno|Laura|L| Conejero|Salvador|S| Peloso|Riccardo|R| López-Serrano|Joaquín|J| Maya|Celia|C| Carmona|Ernesto|E|

metallacycles
DFT
CC coupling
Pt carbenes
agostic interactions


Accelerating Psychological Health Research Findings into Clinical Practice Through the Practice-Based Implementation Network Model.

Abstract: The benefits of new clinical research developments often take years to reach patients. As such, the Departments of Defense (DoD) and Veterans Affairs built the Practice-Based Implementation (PBI) Network as an infrastructure to facilitate more rapid translation of psychological health (PH) research into clinical practice changes to improve the quality of care for military and Veteran patients. To regularly identify research findings appropriate for enterprise implementation, the DoD PBI Network developed a model aligned with the Consolidated Framework for Implementation Research to select and pilot PH practice change. Within this model, practice change pilots were selected following a survey of field clinicians, a public call for proposals, annual meeting of implementation science subject matter experts, and final pilot selection by PH strategic leaders. These components facilitated commitment and engagement from Military Health System PH leadership, as well as clinicians, leading to increased stakeholder buy-in and efficiency with selecting and piloting PH practice change. The DoD PBI Network model has been refined for future PH research translation pilots. It serves as a first operational model for annual implementation of PH research findings in the DoD and may be of use to other entities engaged in practice change implementation.

Creason|Alia H|AH|
Ruscio|Aimee C|AC|
Tate|Karyn E|KE|
McGraw|Kate L|KL|

psychological health
practice change
military
implementation science
research translation


Review of phosphorus attenuation in groundwater plumes from 24 septic systems.

Abstract: This study reviews phosphorus (P) concentrations in groundwater plumes from 24 on-site wastewater treatment systems (septic systems) in Ontario, Canada. Site investigations were undertaken over a 30-year period from 1988 to 2018 at locations throughout the province that encompass a variety of domestic wastewater types and geologic terrain. The review focuses on P behaviour in the drainfield sediments and in the proximal plume zones, within 10 m of the drainfields, where plume conditions were generally at steady state. At these sites, mean soluble reactive phosphorus (SRP) values in the septic tank effluent ranged from 1.8 to 13.8 mg/L and averaged 8.4 mg/L. Phosphorus removal in the drainfields averaged 90% at sites where sediments were non calcareous (13 sites) and 66% at sites where sediments were calcareous (11 sites). Removal considering both the drainfields and proximal plume zones, averaged 97% at the non-calcareous sites and 69% at the calcareous sites, independent of the site age or loading rate. At 17 of the 24 sites, mean SRP concentrations in the proximal groundwater plumes (within 10 m) declined to ≤1 mg/L, which is a common treatment level for P at sewage treatment plants. Zones of P accumulation were present in almost all of the drainfields, where sand grains exhibited distinct secondary coatings containing P, demonstrating that mineral precipitation was likely the dominant cause of the P retention observed at these sites. This review confirms the often robust capacity for phosphorus removal in properly functioning septic systems. At the majority of these sites (17/24), P retention meets or exceeds removal that would normally be achieved during conventional sewage treatment. This challenges the necessity of avoiding septic system use in favor of communal sewer systems, when limiting phosphorus loading to nearby water courses is a principal or major concern.

Robertson|William D|WD|
Van Stempvoort|Dale R|DR|
Schiff|Sherry L|SL|


Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine.

Abstract: Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.

Kale|Atharva|A|
Rogers|Natasha M|NM|
Ghimire|Kedar|K|0000-0002-4672-5256

D051928:CD47 Antigen
D002450:Cell Communication
D006801:Humans
D007668:Kidney
D007674:Kidney Diseases
D008659:Metabolic Diseases
D009369:Neoplasms
D015398:Signal Transduction
D019700:Thrombospondin 1
D014652:Vascular Diseases

thrombospondin-1 (TSP1
CD47 (IAP)
THBS1)
ageing
fibrosis
glucose homeostasis
kidney injury
matricellular
reactive oxygen species


Olive oil by-product as functional ingredient in bakery products. Influence of processing and evaluation of biological effects.

Abstract: Nowadays, the strong demand for adequate nutrition is accompanied by concern about environmental pollution and there is a considerable emphasis on the recovery and recycling of food by-products and wastes. In this study, we focused on the exploitation of olive pomace as functional ingredient in biscuits and bread. Standard and enriched bakery products were made using different flours and fermentation protocols. After characterization, they were in vitro digested and used for supplementation of intestinal cells (Caco-2), which underwent exogenous inflammation. The enrichment caused a significant increase in the phenolic content in all products, particularly in the sourdough fermented ones. Sourdough fermentation also increased tocol concentration. The increased concentration of bioactive molecules did not reflect the anti-inflammatory effect, which was modulated by the baking procedure. Conventionally fermented bread enriched with 4% pomace and sourdough fermented, not-enriched bread had the greatest anti-inflammatory effect, significantly reducing IL-8 secretion in Caco-2 cells. The cell metabolome was modified only after supplementation with sourdough fermented bread enriched with 4% pomace, probably due to the high concentration of tocopherol that acted synergistically with polyphenols. Our data highlight that changes in chemical composition cannot predict changes in functionality. It is conceivable that matrices (including enrichment) and processing differently modulated bioactive bioaccessibility, and consequently functionality.

Di Nunzio|Mattia|M|
Picone|Gianfranco|G|
Pasini|Federica|F|
Chiarello|Elena|E|
Caboni|Maria Fiorenza|MF|
Capozzi|Francesco|F|
Gianotti|Andrea|A|
Bordoni|Alessandra|A|

Olive oil by-products
Bakery
Fermentation
Inflammation
Polyphenols
Cultured intestinal cells
Foodomics
NMR based metabolomics


Primary Imaging Test for Suspected Traumatic Thoracolumbar Spine Injury: 2017 Guidelines by the Korean Society of Radiology and National Evidence-Based Healthcare Collaborating Agency.

Abstract: The Korean Society of Radiology and the National Evidence-based Healthcare Collaborating Agency developed a primary imaging test for suspected traumatic thoracolumbar spine injury. This guideline was developed using an adaptation process involving collaboration between the development committee and the working group. The development committee, consisting of research methodology experts, established the overall plan and provided support on research methodology. The working group, composed of radiologists with expertise in musculoskeletal imaging, wrote the recommendation. The guidelines recommend that thoracolumbar spine computed tomography without intravenous contrast enhancement be the first-line imaging modality for diagnosing traumatic thoracolumbar spine injury in adults.

Lee|Guen Young|GY|0000-0002-6906-5182
Hwang|Ji Young|JY|0000-0001-5848-3429
Kim|Na Ra|NR|
Kang|Yusuhn|Y|
Choi|Miyoung|M|
Kim|Jimin|J|
Ha|Eun Ju|EJ|
Baek|Jung Hwan|JH|

D000328:Adult
D003287:Contrast Media
D055317:Evidence-Based Practice
D017408:Guidelines as Topic
D006801:Humans
D008159:Lumbar Vertebrae
D011859:Radiography
D056910:Republic of Korea
D013124:Spinal Injuries
D013904:Thoracic Vertebrae
D014057:Tomography, X-Ray Computed

Spine
Injury
Guideline
Computed tomography
Magnetic resonance imaging
Radiography
Trauma


The association between IL18, FOXP3 and IL13 genes polymorphisms and risk of allergic rhinitis: a meta-analysis.

Abstract:
OBJECTIVES
Allergic rhinitis (AR) is a chronic inflammatory disease of nasal mucosa. Loss of function of Th17 cells and regulatory T (Treg) cells plays a role in the pathogenesis of AR. IL18, FOXP3, and IL13 are key genes in the development of AR. However, the genetic associations between IL18, FOXP3 and IL13 genes polymorphisms and AR risk were inconclusive yet.

METHODS
A meta-analysis was performed by searching through Pubmed, EMBASE, web of science and CNKI databases. The ORs and 95%CIs were used to assess the genetic association between the allelic, dominant and recessive models of IL18, FOXP3 and IL13 genes polymorphisms and AR risk.

RESULTS
A total of 15 articles (6 for FOXP3, 5 for IL18, and 5 for IL13) were enrolled in the present study. No association was detected between the IL18 rs187238, rs1946518, rs360721, FOXP3 rs2232365, rs3761548 and IL13 rs1800925 polymorphisms and AR risk (p > 0.05). Significant associations were observed between the allelic (p = 0.001, OR 1.32, 95% CI 1.12-1.56), dominant (p = 0.005, OR 1.43, 95% CI 1.11-1.83) and recessive models (p = 0.01, OR 1.64, 95% CI 1.13, 2.40) of IL13 rs20541 and AR risk. Subgroup analysis based on ethnicity revealed that the IL13 rs20541 was significantly associated with AR risk in Asian population (allelic model: p = 0.009, OR 1.36, 95% CI 1.13-1.63, dominant model: p = 0.005, OR 1.43, 95% CI 1.11-1.83; recessive model: p = 0.01, OR 1.64, 95% CI 1.13-2.40).

CONCLUSIONS
IL13 rs20541 may contribute to the risk of AR in Asian population. To confirm these results, larger number of case-control study with more subjects is necessary in the future.

D020022:Genetic Predisposition to Disease


Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.

Abstract:
OBJECTIVE
Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23.

METHODS
Peripheral blood monocyte isolated from 10 HLA-B27+ patients and five HLA-B27+ normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR.

RESULTS
RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant.

CONCLUSIONS
Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.

Rezaiemanesh|Alireza|A|
Mahmoudi|Mahdi|M|
Amirzargar|Ali Akbar|AA|
Vojdanian|Mahdi|M|
Jamshidi|Ahmad Reza|AR|
Nicknam|Mohammad Hossein|MH|


Concentrated growth factor in the treatment of adjacent multiple gingival recessions: a split-mouth randomized clinical trial.

Abstract:
AIM
The aim of this study was to determine the clinical effect of concentrated growth factor (CGF) in combination with coronally advanced flap (CAF) compared to CAF alone for the treatment of multiple adjacent gingival recessions (GRs).

MATERIALS AND METHODS
Twenty patients with a total of 119 Miller Class I and II GRs in the maxilla were included to this study. Recessions were randomly treated according to a split-mouth design by means of CAF + CGF (test; 60 defects) or CAF (control; 59 defects). Clinical outcomes were evaluated at baseline and 6 months after surgery.

RESULTS
The mean root coverage (MRC) was 82.06% and 86.67%, complete root coverage (CRC) was 45.8% (27/59) and 56.7% (34/60) for CAF and CAF + CGF, respectively at 6th month. Statistically no difference was demonstrated between the two groups in terms of recession depth (RD), MRC and CRC at 6th month. The increase in width of keratinized gingiva (KGW) and gingival thickness (GT) were statistically significant in the CAF + CGF group compared to the CAF group at 6th month.

CONCLUSIONS
The use of CGF in combination with CAF did not provide additional benefits in RD, CRC and MRC. This study suggests that use of CGF + CAF may increase the success of GRs because of a significant increase in KGW and GT.

Bozkurt Doğan|Şeyma|Ş|
Öngöz Dede|Figen|F|
Ballı|Umut|U|
Atalay|Elif N|EN|
Durmuşlar|Mustafa C|MC|

D036341:Intercellular Signaling Peptides and Proteins

concentrated growth factor
growth factor
gingival recession
root coverage
plastic surgery
platelet-rich fibrin


Microglia in the normally aged hippocampus.

Abstract: The hippocampus plays important roles in the regulation and combination of short and long term memory and spatial navigation with other brain centers. Aging is accompanied by a functional decline of the hippocampus and degenerative disease. Microglia are major immune cells in the central nervous system and response to degenerative changes in the aged brain. In this respect, functional and morphological changes of the hippocampus have been closely related to microglial changes during normal aging with or without disease. Therefore, in this review, we discuss morphological and functional changes of the hippocampus and microglia in the aging brain.


Segmentation of gray matter, white matter, and CSF with fluid and white matter suppression using MP2RAGE.

Abstract:
BACKGROUND
MP2RAGE can generate uniform T1 -weighted images, which have been used for brain segmentation. However, there remain concerns about carrying out fast brain segmentation.

PURPOSE
To propose an acquisition-based method for fast segmentation of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) of healthy human brains with fluid and white matter suppression (FLAWS) using MP2RAGE.

STUDY TYPE
Prospective.

SUBJECTS
12 volunteers (23-28 years, seven subjects; 51-62 years, five subjects).

FIELD STRENGTH/SEQUENCES
3T/3D MPRAGE and FLAWS.

ASSESSMENT
The proposed method was evaluated by calculating tissue volumes and the spatial overlap with the segmentation results from FSL and SPM12. The processing time was recorded.

STATISTICAL TESTS
A paired t-test was used to compare the tissue volumes of the proposed method with those from other segmentation methods RESULTS: For the 12 subjects, the tissue volume difference between the proposed and SPM12 were 3.2 ± 2.8%, 4.2 ± 2.5%, 18.2 ± 13.1% for GM, WM, and CSF, respectively. The relative difference between the proposed and FSL was over 14% for all tissue classes. The spatial overlap between the proposed and other methods were 87-94% for GM and WM and less than 80% for CSF. The GM and WM volumes of the proposed method were not significantly different from those of SPM12 using MPRAGE as the input (P = 0.5540 and P = 0.3115, respectively). The rest of the comparisons all showed significant differences between the proposed and other methods. Statistical analysis of the two subgroups yielded similar results. The mean processing time of one subject was 6.5, 185, and 165 seconds for the proposed method, FSL, and SPM12, respectively.

DATA CONCLUSION
Our method may be accurate for the segmentation of most brain structures using FLAWS. In addition, the proposed method is fast and applicable to the two distinct age ranges.

LEVEL OF EVIDENCE
2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1540-1550.

Wang|Yishi|Y| Wang|Yajie|Y| Zhang|Zhe|Z| Xiong|Yuhui|Y| Zhang|Qiang|Q| Yuan|Chun|C| Guo|Hua|H|


Conversion of aliphatic nitriles by the arylacetonitrilase from Pseudomonas fluorescens EBC191.

Abstract: The conversion of aliphatic nitriles by the arylacetonitrilase from Pseudomonas fluorescens EBC191 (NitA) was analyzed. The nitrilase hydrolysed a wide range of aliphatic mono- and dinitriles and showed a preference for unsaturated aliphatic substrates containing 5-6 carbon atoms. In addition, increased reaction rates were also found for aliphatic nitriles carrying electron withdrawing substituents (e.g. chloro- or hydroxy-groups) close to the nitrile group. Aliphatic dinitriles were attacked only at one of the nitrile groups and with most of the tested dinitriles the monocarboxylates were detected as major products. In contrast, fumarodinitrile was converted to the monocarboxylate and the monocarboxamide in a ratio of about 65:35. Significantly different relative amounts of the two products were observed with two nitrilase variants with altered reaction specifities. NitA converted some aliphatic substrates with higher rates than 2-phenylpropionitrile, which is one of the standard substrates for arylacetonitrilases. This indicated that the traditional classification of nitrilases as "arylacetonitrilases", "aromatic" or "aliphatic" nitrilases might require some corrections. This was also suggested by the construction of some variants of NitA which were modified in an amino acid residue which was previously suggested to be essential for the conversion of aliphatic substrates by a homologous nitrilase.

Nitrilase
Biotransformation
Regioselective hydrolysis
Substrate specifity


Methods of knowledge discovery in tweets.

Abstract: 1) to describe web mining methods for knowledge discovery in Tweets, and 2) to illustrate application of the methods using the topic of physical activity. Methods described include: 1) structure mining to discover structures (macro-, meso-, and micro-level) of Tweet networks using social network analysis, and 2) content mining to discover Tweet contents using n-gram based text analysis and sentiment analysis. Specific web mining tools for each step of the web mining process (e.g., NodeXL, ORA, Pajek, Weka) are detailed. Our novel application of web mining methods was useful in understanding multiple dimensions of physical activity. The methods that we applied may be useful to others wishing to mine social media for health-related purposes.

knowledge discovery
web mining
structure mining
content mining
Twitter
web 2.0


The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients.

Abstract:
INTRODUCTION
The host response to septic shock is dynamic and complex. A sepsis-induced immunosuppression phase has recently been acknowledged and linked to bad outcomes and increased healthcare costs. Moreover, a marked suppression of the immune response has also been partially described in patients hospitalized in intensive care unit (ICU) for severe trauma or burns. It has been hypothesized that immune monitoring could enable identification of patients who might most benefit from novel, adjunctive immune-stimulating therapies. However, there is currently neither a clear definition for such injury-induced immunosuppression nor a stratification biomarker compatible with clinical constraints.

METHODS AND ANALYSIS
We set up a prospective, longitudinal single-centre clinical study to determine the incidence, severity and persistency of innate and adaptive immune alterations in ICU patients. We optimized a workflow to describe and follow the immunoinflammatory status of 550 patients (septic shock, severe trauma/burn and major surgery) during the first 2 months after their initial injury. On each time point, two immune functional tests will be performed to determine whole-blood TNF-α production in response to ex vivo lipopolysaccharide stimulation and the T lymphocyte proliferation in response to phytohaemagglutinin. In addition, a complete immunophenotyping using flow cytometry including monocyte HLA-DR expression and lymphocyte subsets will be obtained. New markers (ie, levels of expression of host mRNA and viral reactivation) will be also evaluated. Reference intervals will be determined from a cohort of 150 age-matched healthy volunteers. This clinical study will provide, for the first time, data describing the immune status of severe ICU patients over time.

ETHICS AND DISSEMINATION
Ethical approval has been obtained from the institutional review board (no 69HCL15_0379) and the French National Security agency for drugs and health-related products. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.

TRIAL REGISTRATION NUMBER
Clinicaltrials.gov Registration number: NCT02638779. Pre-results.

Rol|Mary-Luz|ML| Venet|Fabienne|F| Rimmele|Thomas|T| Moucadel|Virginie|V| Cortez|Pierre|P| Quemeneur|Laurence|L| Gardiner|David|D| Griffiths|Andrew|A| Pachot|Alexandre|A| Textoris|Julien|J|0000-0002-3821-9337 Monneret|Guillaume|G| |||

D056704:Adaptive Immunity
D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D015415:Biomarkers
D049109:Cell Proliferation
D002478:Cells, Cultured
D000068456:Clinical Studies as Topic
D016638:Critical Illness
D005260:Female
D006801:Humans
D007108:Immune Tolerance
D007113:Immunity, Innate
D016130:Immunophenotyping
D007362:Intensive Care Units
D008070:Lipopolysaccharides
D008137:Longitudinal Studies
D008297:Male
D008875:Middle Aged
D010937:Plant Growth Regulators
D011446:Prospective Studies
D012107:Research Design
D012772:Shock, Septic
D013514:Surgical Procedures, Operative
D013601:T-Lymphocytes
D014409:Tumor Necrosis Factor-alpha
D014947:Wounds and Injuries
D055815:Young Adult

Injury-induced immunosuppression
Intensive care unit
Biomarkers
Adaptive immunity
Healthcare-associated infections
Innate immunity


Association of late-life depression with cognitive impairment: evidence from a cross-sectional study among older adults in India.

Abstract:
BACKGROUND
Late-life depression (LLD) is considered as a prodrome to dementia and plays a major role in the development of long-term cognitive disabilities. We aimed to estimate the prevalence and correlates of LLD and cognitive impairment and to explore their associations among older adults in India.

METHODS
Data for this study was derived from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017-18). The total sample included 31,464 (15,098 male and 16,366 female) older individuals aged 60 years and above. Cognitive impairment measured from various domains derived from the cognitive module of the Health and Retirement Study (HRS), and major depression measured by the CIDI-SF (Composite International Diagnostic Interview- Short Form) were the outcome variables. Descriptive, bivariate, and multivariable analyses were performed to fulfill the objectives of the study.

RESULTS
The overall prevalence of LLD and cognitive impairment for the current sample was 8.7% and 13.7 % respectively. Among older individuals who have rated their health status as poor were 2.59 times more likely to suffer from LLD [OR: 2.59, CI: 2.24-2.99] as compared to their counterparts. The older adults who had difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL) were 74% and 69 % more likely to suffer from LLD. Similarly, older adults who were depressed had higher odds of cognitive impairment [OR: 1.22, CI: 1.01-1.48] compared to their counterparts. Also, older adults who were depressed and belonged to rural areas were 2.58 times [AOR: 2.58, CI: 1.95-3.41] more likely to be cognitively impaired than those who were not depressed and resided in urban areas.

CONCLUSIONS
Depression is linked to an increased risk of cognitive decline and dementia; therefore, failing to diagnose and treat LLD in later life may have significant health implications. Moreover, treatment under the care of a cognitive neurologist or geriatric psychiatrist is recommended for people with LLD and cognitive disability due to both the disorders' complex existence.

Depression
Cognitive impairment
Older adults
India


Early Injection of Furosemide Increases Detection Rate of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT.

Abstract: The aim of this study was twofold. First, we aimed to assess the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of 68Ga-PSMA-11 before it binds to the PSMA receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Methods: In a retrospective analysis, 2 different groups with 220 prostate cancer patients each, referred for 68Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients in group 1 (median prostate-specific antigen, 1.30 ng/mL) received no preparation before imaging, whereas patients in group 2 (median prostate-specific antigen, 0.82 ng/mL) were injected with 20 mg of furosemide and 500 mL of sodium chloride (NaCl 0.9%) immediately after tracer injection. The presence of local recurrence was assessed visually. In addition, the intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide than in patients without preparation: 56 cases (25.5%) versus 38 cases (17.3%), respectively (P = 0.048). Median maximum SUVs (SUVmax) of organs with physiologic uptake of 68Ga-PSMA-11 in groups 1 and 2 were urinary bladder (63.0 vs. 8.9), kidney (55.6 vs. 54.5), liver (9.9 vs. 9.4), spleen (11.2 vs. 11.9), small bowel (16.2 vs. 17.1), parotid gland (19.2 vs. 19.6), lacrimal gland (8.9 vs. 10.9), blood-pool activity (2.2 vs. 2.3), muscle (1.0 vs. 1.1), and bone (1.6 vs. 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg of furosemide at the time point of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-PSMA-11 PET/CT. As intensity of 68Ga-PSMA-11 uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of 68Ga-PSMA-11 seems unlikely.

Uprimny|Christian|C|
Bayerschmidt|Steffen|S|
Kroiss|Alexander Stephan|AS|
Fritz|Josef|J|
Nilica|Bernhard|B|
Svirydenka|Hanna|H|
Decristoforo|Clemens|C|
von Guggenberg|Elisabeth|E|
Horninger|Wolfgang|W|
Virgolini|Irene Johanna|IJ|

furosemide
local recurrence
prostate cancer
biochemical recurrence
68Ga-PSMA-11
PET
PET/CT
forced diuresis
prostate specific membrane antigen


Detection of Risk Groups for Carcinogenic Liver Fluke Infection by Verbal Screening Questionnaire Using a Mobile Application

Abstract:
The carcinogenic liver fluke, Opisthorchis viverrini, is a serious health problem in Southeast Asia where infection
is associated with cholangiocarcinoma, a major cause of death in Thailand. This cross-sectional study aimed to screen
for O. viverrini infection among a Thai rural population of 560 individuals from Nakhon Ratchasima, Khonkaen, and
Chaiyaphum provinces with a verbal screening test with a mobile application (OvApp). Faecal samples were also
processed with a mini-parasep sf parasite faecal concentrator. The infection rate of O. viverrini was found to be 2.86%.
The majority of infections were detected in males aged 41–50, with primary school being their highest education level, and
who were engaged in agricultural occupations. In screening for O. viverrini infection, the OvApp had a high sensitivity
(87.5%), specificity (94.6%), negative predictive value (98.9%), and accuracy (98.6%). The positive predictive value
was 70.0% for the OvApp. The observed agreement was substantial for this application (k-value = 0.64) indicated that
it is a potentially useful tool for decreasing the cost of large-scale O. viverrini screening.

Kaewpitoon|Natthawut|N|
Kaewpitoon|Soraya J|SJ|
Meererksom|Thirayu|T|
Chan-Aran|Siwawich|S|
Sangwalee|Wararat|W|
Kujapun|Jirawoot|J|
Norkaew|Jun|J|
Chuatanam|Jirayut|J|
Ponpimai|Sukanya|S|
Pothipim|Mali|M|
Padchasuwan|Natnapa|N|
Tongtawee|Taweesak|T|
Matrakool|Likit|L|
Panpimanmas|Sukij|S|
Loyd|Ryan A|RA|
Wakkhuwatthapong|Parichart|P|

verbal screening questionnaire
Opisthorchis viverrini
Thailand
mobile application
OvApp


Estimating the burden of irritable bowel syndrome: analysis of a nationwide korean database.

Abstract:
BACKGROUND/AIMS
Management of irritable bowel syndrome (IBS) imposes a heavy economic burden. This study was to estimate the epidemio-logic features of IBS and to report the IBS burden for the first time in the Korean population.

METHODS
A cross-sectional study was conducted using the National Health Insurance (NHI) system database, which covers the entire pop-ulation of Korea. IBS was defined as diagnostic code -10 in adults with any outpatient clinic visits or hospitalization related to IBS. We excluded diseases that mimic IBS symptoms.

RESULTS
A total of 2.42 million (58.2% female) individuals were identified as patients with IBS, yielding an age- and gender-adjusted prevalence of 5.1% in males and 6.9% in females. The prevalence of IBS increased proportionally with age, with higher medical costs in middle-aged patients. Outpatient clinics were visited by 98.6% of IBS patients, and 1.9% were treated upon admission. Of these patients, 87.6% were given a prescription. Co-morbidities that commonly accompanied IBS included upper gastro-intestinal (36.1%), respiratory (12.3%), musculoskeletal (8.0%) disease, somatoform (4.3%) and depression/anxiety disorders (3.1%). The NHI costs of IBS, which include the NHI covered cost and beneficiary copayment charges, were estimated to be 155 million USD, which accounts for 0.46% of the total NHI costs for the entire Korean population.

CONCLUSIONS
According to the Korean national claims database, about 6% of the Korean population seeks medical care for IBS at least once per year. This high prevalence places a large economic burden on the Korean healthcare system, accounting for 0.46% of over-all national medical expenditure.

Jung|Hye-Kyung|HK|
Kim|Youn Hee|YH|
Park|Joo Yeon|JY|
Jang|Bo Hyoung|BH|
Park|Sun-Young|SY|
Nam|Mi-Hee|MH|
Choi|Myung-Gyu|MG|

Irritable bowel syndrome
Population
Cost of illness
Epidemiology


A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET.

Abstract: MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.

Li|Jing|J| Tan|Guishan|G| Cai|Yabo|Y| Liu|Ruihuan|R| Xiong|Xiaolin|X| Gu|Baohua|B| He|Wei|W| Liu|Bing|B| Ren|Qingyun|Q| Wu|Jianping|J| Chi|Bo|B| Zhang|Hang|H| Zhao|Yanzhong|Y| Xu|Yangrui|Y| Zou|Zhenxing|Z| Kang|Fenghua|F| Xu|Kangping|K|

D015972:Gene Expression Regulation, Neoplastic

Apigenin derivatives
Renal cell carcinoma
MET
Drug-resistant MET mutations
MET downstream signaling


Promoting independence in Lewy body dementia through exercise (PRIDE) study: Protocol for a pilot study.

Abstract:
Background
Lewy Body dementia (LBD) is the second most prevalent neurodegenerative dementia. This form of dementia is notable for an aggressive disease course consisting of a combination of cognitive, Parkinsonian, affective, and physiological symptoms that significantly increase morbidity and mortality, and decrease life expectancy in this population compared to more common dementias. Additionally, those diagnosed with LBD are often excluded from trials evaluating exercise in similar diseases such as Alzheimer's disease or Parkinson's disease due to the complexity and concurrency of motor and cognitive symptoms. Consequently, there is scarce research evaluating the effect of exercise on individuals with LBD.

Methods
The PRomoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial is a novel non-randomised, crossover pilot study consisting of an 8-week wait-list usual care period, followed by an 8-week exercise intervention targeting progressive resistance and balance training. The trial aim is to evaluate the effect of exercise on the primary outcome of functional independence and secondary outcomes including cognitive, physical, psychosocial and quality of life measures in people living with LBD and their caregivers. The intervention involves 3 supervised 1-h sessions per week (24 sessions in total) administered by an Accredited Exercise Physiologist in a clinical facility at the University of Sydney in Lidcombe, Australia.

Discussion
The PRIDE study is the first controlled trial to evaluate a robust exercise intervention within a LBD cohort and will provide crucial information required to inform robust future clinical trials.

Trial registration
Australia and New Zealand Trial Register (ANZCTR): ACTRN12616000466448; Key words: Lewy body; dementia; exercise; anabolic; functional independence.

Inskip|Michael|M|
Mavros|Yorgi|Y|
Sachdev|Perminder S|PS|
Fiatarone Singh|Maria A|MA|

Lewy body
Dementia
Exercise
Functional independence
Anabolic


Complications in type III open tibial shaft fractures treated with open reduction and internal fixation.

Abstract: Aim: To estimate rates of fracture-related infection (FRI) and nonunion and assess the healthcare burden associated with FRI among patients with open reduction and internal fixation (ORIF) for Type III open tibial shaft fractures (TSFs). Methods: Patients with type III TSF requiring ORIF were identified using MarketScan® Database. Healthcare utilization and total costs were compared using generalized linear models. Results: The rates of FRI and nonunion were 35.99 and 36.94%, respectively, at 365 days. Patients with FRI had a significantly higher rate of readmission, emergency room visit and total healthcare costs compared with patients without FRI. Conclusion: Patients with an ORIF procedure for Type III TSF have a high risk of FRI and nonunion and; FRI significantly increased the healthcare burden.

D000293:Adolescent
D000328:Adult
D016208:Databases, Factual
D005260:Female
D005593:Fracture Fixation, Internal
D005102:Health Expenditures
D006296:Health Services
D006801:Humans
D008297:Male
D008875:Middle Aged
D000070799:Open Fracture Reduction
D012189:Retrospective Studies
D013978:Tibial Fractures
D015599:Trauma Severity Indices
D016896:Treatment Outcome
D055815:Young Adult

Gustilo Anderson Type III open fractures


Oxytocin and emergency caesarean section in a mediumsized hospital in Pakistan: A cross-sectional study.

Abstract:
INTRODUCTION
One of the most common complications during labor is prolonged labor (dystocia), which is associated with risks for the mother and fetus. Dystocia is usually treated with oxytocin, which is also used to induce labor. Oxytocin may not have the desired effect of progress and can negatively affect the fetus, thus resulting in an emergency caesarean section (CS). The aim of this study was to describe obstetric practice, use of oxytocin and its association with an emergency CS.

METHODS
A cross-sectional retrospective register study was conducted that included all women who gave birth during 2014 and 2015 at a hospital in a large city in Pakistan.

RESULTS
A total of 6652 women gave birth to 6767 newborns, 66.8% were multiparous and 33.2% primiparous women. Of the primiparous women, 78.9% had a spontaneous vaginal birth, 1.2% an elective CS and 14.4% an emergency CS. Of the multiparous women, 81.9% had a spontaneous vaginal birth, 8.0% an elective CS and 6.7% an emergency CS. Operative vaginal birth was 2.1% among primiparous and 0.2% among multiparous women. Oxytocin for induction or augmentation was administered to 60.0% of primiparous and 30.5% of multiparous women. Oxytocin during the first stage of labor was associated with an increased risk for emergency CS for both primiparous and multiparous women.

CONCLUSIONS
Despite the association between oxytocin and emergency CS, the CS rate was low in this hospital. The majority of the women gave birth vaginally, even with a breech presentation. Few operative vaginal births were performed.

Lukasse|Mirjam|M| Hovda|Ingrid|I| Thommessen|Sara|S| McAuley|Sosan|S| Morrison|Marian|M|

oxytocin
caesarean section
Pakistan
obstetric practice
Low-MiddleIncome countries


Complete genome of Bacillussubtilis subsp. subtilis KCTC 3135T and variation in cell wall genes of B. subtilis strains.

Abstract: The type strain Bacillus subtilis subsp.subtilis KCTC 3135T was deeply sequenced and annotated, replacing a previous draft genome in this study. The tar and tag genes were involved in synthesizing wall teichoic acids (WTAs), and these genes and their products were previously regarded as the distinguishing difference between B. s. subtilis and B. s. spizizenii. However, a comparative genomic analysis of B. subtilis spp. revealed that both B. s. subtilis and B. s. spizizenii had various types of cell walls. These tar and tag operons were mutually exclusive and the tar genes from B. s. spizizenii were very similar to the genes from non-Bacillus bacteria, unlike the tag genes from B. s. subtilis. The results and previous studies suggests that the tar genes and the tag genes are not inherited after subspecies speciation. The phylogenetic tree based on whole genome sequences showed that each subspecies clearly formed a monophyletic group, while the tree based on tar genes showed that monophyletic groups were formed according to the cell wall type rather than the subspecies. These findings indicate that the tar genes and the presence of ribitol as a cell-wall constituent were not the distinguishing difference between the subspecies of B. subtilis and that the description of subspecies B. s. spizizenii should be updated.

Ahn|Seonjoo|S|
Jun|Sangmi|S|
Ro|Hyun-Joo|HJ|
Kim|Ju Han|JH|
Kim|Seil|S|


Testing early warning metrics for drought-induced tree physiological stress and mortality.

Abstract: Climate change-driven drought stress has triggered numerous large-scale tree mortality events in recent decades. Advances in mechanistic understanding and prediction are greatly limited by an inability to detect in situ where trees are likely to die in order to take timely measurements and actions. Thus, algorithms of early warning and detection of drought-induced tree stress and mortality could have major scientific and societal benefits. Here, we leverage two consecutive droughts in the southwestern United States to develop and test a set of early warning metrics. Using Landsat satellite data, we constructed early warning metrics from the first drought event. We then tested these metrics' ability to predict spatial patterns in tree physiological stress and mortality from the second drought. To test the broader applicability of these metrics, we also examined a separate drought in the Amazon rainforest. The early warning metrics successfully explained subsequent tree mortality in the second drought in the southwestern US, as well as mortality in the independent drought in tropical forests. The metrics also strongly correlated with spatial patterns in tree hydraulic stress underlying mortality, which provides a strong link between tree physiological stress and remote sensing during the severe drought and indicates that the loss of hydraulic function during drought likely mediated subsequent mortality. Thus, early warning metrics provide a critical foundation for elucidating the physiological mechanisms underpinning tree mortality in mature forests and guiding management responses to these climate-induced disturbances.

drought
remote sensing
climate change
extreme events
plant hydraulics


The evolution of local food environments within established neighbourhoods and new developments in Perth, Western Australia.

Abstract: Temporal changes in the location of food outlets can result in disparities in the availability and access of food across geographic areas, contributing to health inequalities. This study used mixed linear models to investigate how the location of food outlets around the home evolved over time with respect to area-level socio-economic status (SES) and urban design within established neighbourhoods and new residential developments. Food outlet data (supermarket/greengrocers, convenience stores, café restaurants and takeaway/fast food) were sourced from commercial database listings (SENSIS Pty. Ltd.) in 2004, 2006, 2007, and 2011. Using 2468 addresses from the RESIDential Environments Project (RESIDE), in Perth, Western Australia (WA), a count of each food outlet type and percentage of healthy food outlets within a 1.6 km road network buffer around the home, along with the road network distance to nearest food outlet were generated relative to each address at each time point. Proximity to and count of all food outlets increased over time in both new developments and established neighbourhoods. However, unhealthy food outlets were always in greater numbers and proximity to the home. The percentage of healthy food outlets was significantly greater in established neighbourhoods compared to new developments at all four time points. There were significantly more food outlets, and within closer proximity to the home, in established neighbourhoods compared to new developments at each time point. In established neighbourhoods, there were more convenience stores, takeaway/fast food and café restaurants, a lower percentage of healthy food outlets, and closer proximity to convenience stores in lower compared to high SES areas. In new developments there were significantly less supermarket/greengrocers, a lower percentage of healthy food outlets and greater proximity to takeaway/fast food and café restaurants in low compared to high SES areas. New developments designed according to the WA government's "Liveable Neighbourhoods Community Design Guidelines" policy had significantly more of all food outlets compared to other new developments. As such, people living in new developments, and low SES areas of Perth, may be disadvantaged with poorer access to healthy food outlets and greater exposure to unhealthy food outlets. Future urban planning and policy should focus on providing incentives that support the early development of supermarkets and healthy food outlets within new developments and low SES areas of Perth.

Bivoltsis|Alexia|A|
Trapp|Gina|G|
Knuiman|Matthew|M|
Hooper|Paula|P|
Ambrosini|Gina Leslie|GL|

D000076624:Built Environment
D002958:City Planning
D003132:Commerce
D057140:Fast Foods
D005523:Food Supply
D054625:Healthcare Disparities
D006801:Humans
D012111:Residence Characteristics
D012147:Restaurants
D012959:Socioeconomic Factors
D014904:Western Australia

Food environment
Health inequalities
Socio-economic status
Urban planning policy


Ellagic Acid Suppresses ApoB Secretion and Enhances ApoA-1 Secretion from Human Hepatoma Cells, HepG2.

Abstract: The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.

Ieda|Ayana|A| Wada|Maki|M| Moriyasu|Yuuki|Y| Okuno|Yuuko|Y| Zaima|Nobuhiro|N| Moriyama|Tatsuya|T|0000-0002-6861-926X

D016632:Apolipoprotein A-I
D053299:Apolipoprotein B-100
D006528:Carcinoma, Hepatocellular
D004610:Ellagic Acid
D056945:Hep G2 Cells
D006801:Humans
D008113:Liver Neoplasms
D009363:Neoplasm Proteins

ellagic acid
apoB
secretion
apoA-1
hepatoma
HepG2
HDL
MTP
VLDL


Clinical pharmacology of glucagon-like peptide-1 receptor agonists.

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an important asset in the armamentarium for the treatment of type 2 diabetes mellitus (type 2 DM). Incretin failure is a critical etiopathogenetic feature of type 2 DM, which, if reversed, results in improved glycaemic control. GLP-1 RAs are injectable peptides that resemble the structure and function of endogenous incretin GLP-1, but as they are not deactivated by the dipeptidyl peptidase-4 (DPP-4), their half-life is prolonged compared with native GLP-1. Based on their ability to activate GLP-1 receptor, GLP-1 RAs are classified as short-acting (exenatide twice-daily and lixisenatide once-daily), and long-acting (liraglutide once-daily and the once-weekly formulations of exenatide extended-release, dulaglutide, and albiglutide). Semaglutide, another long-acting, once-weekly GLP-1 RA, was recently approved by the FDA and EMA. Although all of these agents potently reduce haemoglobin A1C (HbA1c), there are unique features and fundamental differences among them related to fasting and postprandial hyperglycaemia reduction, weight loss potency, cardiovascular protection efficacy, and adverse events profile. It is imperative that current evidence be integrated and applied in the context of an individualised patient-centred approach. This should include not only glucose management but also targeting as many as possible of the pathophysiologic mechanisms responsible for type 2 DM development and progression.

Sfairopoulos|Dimitrios|D| Liatis|Stavros|S| Tigas|Stelios|S| Liberopoulos|Evangelos|E|

Type 2 diabetes
Exenatide
Liraglutide
Dulaglutide
Semaglutide
GLP-1 receptor agonists


Molecular Mechanism of Cannabinoids in Cancer Progression.

Abstract: Cannabinoids are a family of heterogeneous compounds that mostly interact with receptors eliciting several physiological effects both in the central and peripheral nervous systems and in peripheral organs. They exert anticancer action by modulating signaling pathways involved in cancer progression; furthermore, the effects induced by their use depend on both the type of tumor and their action on the components of the endocannabinoid system. This review will explore the mechanism of action of the cannabinoids in signaling pathways involved in cancer proliferation, neovascularisation, migration, invasion, metastasis, and tumor angiogenesis.

Pagano|Cristina|C| Navarra|Giovanna|G| Coppola|Laura|L| Bifulco|Maurizio|M| Laezza|Chiara|C|

cannabinoids
cancer
migration
angiogenesis
cell death


Prognostic significance of extensive versus limited induction protocol during catheter ablation of scar-related ventricular tachycardia.

Abstract:
INTRODUCTION
Testing for inducible ventricular tachycardia (VT) pre- and postablation forms the cornerstone of contemporary scar-related VT ablation procedures. There is significant heterogeneity in reported VT induction protocols. We examined the utility of an extensive induction protocol (up to 4 extra-stimuli [ES] ± burst ventricular pacing) compared to the current guideline-recommended protocol (up to 3ES, defined as limited induction protocol) in patients with scar-related VT.

METHODS AND RESULTS
Sixty-two patients (age: 64 ± 14 years; left ventricular ejection fraction: 37 ± 13%, ischemic cardiomyopathy: 31, nonischemic cardiomyopathy: 31) with at least one inducible VT were included. An extensive testing protocol induced 11%-17% more VTs, compared to the limited induction protocol before, and after the final ablation. VT recurred in 48% of patients during a mean follow up of 566 ± 428 days. Patients who were noninducible for any VT using the limited induction protocol had worse ventricular arrhythmia (VA)-free survival (12 months, 43% vs. 82%; p = .03) and worse survival free of VA, transplantation and mortality (12 months 46% vs. 82%; p = .02), compared to patients who were noninducible for any VT using the extensive induction protocol.

CONCLUSIONS
Between 11% and 17% of inducible VTs may be missed if 4ES and burst pacing are not performed in induction protocols before and after ablation. Noninducibility for any VT after an extensive induction protocol after the final ablation portends more favorable prognostic outcomes when compared with the current guideline-recommended induction protocol of up to 3ES. This data suggests that the adoption of an extensive induction protocol is of prognostic benefit after VT ablation.

induction protocol
catheter ablation
ventricular tachycardia
inducibility
ischemic cardiomyopathy
nonischemic cardiomyopathy
burst pacing


Clinical validity of a brief measure of early childhood social-emotional/behavioral problems.

Abstract:
OBJECTIVE
To address a pressing need for measures of clinically significant social-emotional/behavioral problems in young children by examining several validity indicators for a brief parent-report questionnaire.

METHODS
An ethnically and economically diverse sample of 213 referred and nonreferred 2- and 3-year-olds was studied. The validity of the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) Problem Index and Internalizing and Externalizing scales was evaluated relative to a "gold standard" diagnostic interview, as well as the Child Behavior Checklist (CBCL).

RESULTS
The validity of the BITSEA Problem Index relative to Diagnosis (sensitivity = 72.7%-80.8%, specificity = 70.0%-83.3%) and clinical-range CBCL scores (sensitivity = 80.0%-96.2%, specificity = 75.0%-89.9%) was supported in the full sample and within minority/nonminority groups. Additional results supported the validity of the BITSEA Internalizing and Externalizing scales.

CONCLUSIONS
Documented validity suggests that the BITSEA may be a valuable tool to aid screening, identification, and assessment efforts targeting early-emergent social-emotional/behavioral problems. Practical implications and generalizability are discussed.

Briggs-Gowan|Margaret J|MJ|
Carter|Alice S|AS|
McCarthy|Kimberly|K|
Augustyn|Marilyn|M|
Caronna|Elizabeth|E|
Clark|Roseanne|R|

D011569:Psychiatric Status Rating Scales

early childhood
assessment
screening
psychiatric diagnosis
social–emotional/behavioral problems
surveillance


Regulation of Glycogen Content in Astrocytes via Cav-1/PTEN/AKT/GSK-3β Pathway by Three Anti-bipolar Drugs.

Abstract: Here we present the data indicating that chronic treatment with three antibipolar drugs, lithium, carbamazepine and valproic acid regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultured astrocytes. All three drugs down-regulate gene expression of Caveoline 1 (Cav-1), decrease membrane content of phosphatase and tensin homolog (PTEN), increase activity of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serine-threonine kinase (AKT), and elevate glycogen synthase kinase 3β (GSK-3β) phosphorylation thus suppressing its activity. As expected, treatment with any of these three drugs increases glycogen content in astrocytes. Our findings indicate that regulation of glycogen content via Cav-1/PTEN/AKT/GSK-3β pathway by the three anti-bipoar drugs may be responsible for therapeutic effects of these drugs, and Cav-1 is an important signal element that may contribute to pathogenesis of various CNS diseases and regulation of its gene expression may be one of the underlying mechanisms of drug action for antibipolar drugs and antidepressants currently in clinical use.

Jia|Shu|S| Li|Baoman|B| Huang|Jingyang|J| Verkhratsky|Alexei|A| Peng|Liang|L|

D000071679:Glycogen Synthase Kinase 3 beta


What is empathy for?

Abstract: The concept of empathy has received much attention from philosophers and also from both cognitive and social psychologists. It has, however, been given widely conflicting definitions, with some taking it primarily as an epistemological notion and others as a social one. Recently, empathy has been closely associated with the simulationist approach to social cognition and, as such, it might be thought that the concept's utility stands or falls with that of simulation itself. I suggest that this is a mistake. Approaching the question of what empathy is via the question of what it is for, I claim that empathy plays a distinctive epistemological role: it alone allows us to know how others feel. This is independent of the plausibility of simulationism more generally. With this in view I propose an inclusive definition of empathy, one likely consequence of which is that empathy is not a natural kind. It follows that, pace a number of empathy researchers, certain experimental paradigms tell us not about the nature of empathy but about certain ways in which empathy can be achieved. I end by briefly speculating that empathy, so conceived, may also play a distinctive social role, enabling what I term 'transparent fellow-feeling'.

Empathy
Fellow-feeling
Knowing what it’s like


Endocrinological Characteristics of 25 Japanese Patients with CHARGE Syndrome.

Abstract: CHARGE syndrome is a congenital disorder caused by mutation of the chromodomain helicase DNA binding protein 7 (CHD7) gene and is characterized by multiple anomalies including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital and/or urological abnormalities, ear anomalies, and hearing loss. In the present study, 76% of subjects had some type of endocrine disorder: short stature (72%), hypogonadotropic hypogonadism (60%), hypothyroidism (16%), and combined hypopituitarism (8%). A mutation in CHD7 was found in 80% of subjects. Here, we report the phenotypic spectrum of 25 Japanese patients with CHARGE syndrome, including their endocrinological features.

Shoji|Yasuko|Y| Ida|Shinobu|S| Etani|Yuri|Y| Yamada|Hiroyuki|H| Kayatani|Futoshi|F| Suzuki|Yasuhiro|Y| Kosaki|Kenjiro|K| Okamoto|Nobuhiko|N|

CHARGE syndrome
CHD7
endocrinological features


Analysis of pemetrexed-based chemotherapy in the treatment of advanced colorectal cancer.

Abstract:
Background
In this study, we evaluated the therapeutic efficacy and toxicity profile of chemotherapy combinations containing pemetrexed for patients with metastatic colorectal cancer. We investigated the optimal chemotherapy treatment regimen to provide a new option for third-line or after treatment of patients with advanced colorectal cancer.

Methods
A total of 88 eligible patients with metastatic colorectal cancer were included in this study from April 2009 to March 2019 at the Department of Oncology, the First Affiliated Hospital of Nanjing Medical University. The baseline information and treatment outcomes of the patients were collected. Statistical analyses of different chemotherapy regimens focusing on objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity were conducted. The superior treatment regimen was determined, and its clinical outcomes were compared with those of the other treatment combinations to explore the factors that potentially contributed to the curative effect.

Results
The 88 patients in this study received 18 treatment regimens. In total, 53 patients had progressive disease (PD), 34 patients had stable disease (SD), 1 patient was assessed as complete response (CR), and no patients had a partial response (PR). The optimal regimen was pemetrexed + S-1 + bevacizumab. The 21 patients treated with this regimen exhibited a higher DCR [61.90% vs. 32.84%, odds ratio (OR) =3.324; 95% confidence interval (CI): 1.201-9.196, P=0.018] than patients treated with the other chemotherapy regimens. Moreover, the median PFS of this regimen was 4.57 (2.62-6.51) months, which was significantly longer [hazard ratio (HR) =0.566; 95% CI: 0.330-0.971, P=0.039] than the 2.57 (2.18-2.95) months of the other regimens. In terms of toxicity, leukopenia (34.1%) and neutropenia (34.1%) had the highest incidence of all-grade adverse events (AEs). Grade 3-4 AEs included neutropenia (15.9%), leukopenia (11.4%), thrombocytopenia (2.3%), and anemia (1.1%).

Conclusions
The combination of pemetrexed + S-1 + bevacizumab was found to be the optimal treatment regimen. This combination was superior to the other treatment regimens in terms of DCR and PFS with controllable toxicity. These results warrant further prospective exploratory clinical trials for pemetrexed-based chemotherapy in metastatic colorectal cancer.

Yu|Zhengyi|Z| Wang|Jiawei|J| Cai|Xiaomin|X| Gao|Zhenzhen|Z| Wang|Sailan|S| Gu|Yanhong|Y|

advanced colorectal cancer
pemetrexed
Metastatic colorectal cancer
third-line treatment


MicroRNA-638 inhibits cell proliferation by targeting suppress PIM1 expression in human osteosarcoma.

Abstract: MicroRNAs (miRNAs) are a type of small noncoding RNAs that often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the functions and the mechanism of miR-638 in osteosarcoma (OS). The expression of miR-638 in OS and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by CCK8 assay. Different assays, including bioinformatics algorithms, luciferase report assay, and Western blotting, were used to identify the target gene proviral integration site for Moloney murine leukemia virus 1 (PIM1) of miR-638 in OS. The expression of PIM1 in clinical OS tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in OS tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in OS than in NCTs, which may induce the corresponding downregulation of miR-638 in OS. Ectopic expression of miR-638 inhibited OS cell growth in vitro. Subsequently, we identified that PIM1 is the downstream target gene of miR-638 in OS cells, and silencing PIM1 expression phenocopied the inhibitory effect of miR-638 on OS cell proliferation. Furthermore, we observed that PIM1 was overexpressed in OS tissues, and high expression of PIM1 in OS predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor through inhibiting PIM1 expression in OS.

Wang|Xiao-Xu|XX| Liu|Jue|J| Tang|Yi-Min|YM| Hong|Liang|L| Zeng|Zhi|Z| Tan|Guang-Hua|GH|


High-fluoride promoted phagocytosis-induced apoptosis in a matured ameloblast-like cell line.

Abstract: Endocytosis and phagocytosis are important physiologic activities occurring during ameloblast differentiation. We have previously found that excess fluoride inhibited ameloblasts endocytotic functions. Here, we hypothesized that increasing amounts of fluoride may affect ameloblast phagocytotic function during their differentiation. Using cell culture, we first induced maturation of the mouse ameloblast-like LS8 cells by treatment with exogenous retinoic acid (RA) and dexamethasone (DEX). We measured their phagocytotic activity by fluorescent microscopy using a live cell visualization station. We found that ameloblast-like LS8 cells matured with RA/DEX treatment and the increasing amounts of fluoride demonstrated the up-regulated expression of the phagocytotic marker proteins, LAMP1 and CD68. A connection between phagocytosis and apoptosis was confirmed by the increased number of phagocytotic vacuole-like structures and the heterochromatin margination phenomenon observed in the RA/DEX with NaF treatment group. The increase in albumin uptake by ameloblasts was confirmed using whole organ culture of incisor tooth germs. Here, in fluoride treated tooth germs, mature canonical ameloblasts showed greater amounts of albumin uptake, which was accompanied by decreased expression of the anti-apoptosis marker, Bcl-2 along with up-regulated expression of CD68. From these observations, we inferred that high doses of fluoride may cause apoptosis by increasing the phagocytosis of protein particles in mature-stage ameloblasts and loss of Bcl-2 signals might be involved in this process.

Yang|Ting|T|
Zhang|Yanli|Y|
Zheng|Dongdong|D|
Hao|Ying|Y|
Snead|Malcolm L|ML|
Duan|Xiaohong|X|

Maturation Endocytosis Phagocytosis Fluoride Enamel


Irradiation for Quarantine Control of Coffee Berry Borer, Hypothenemus hampei (Coleoptera: Curculionidae: Scolytinae) in Coffee and a Proposed Generic Dose for Snout Beetles (Coleoptera: Curculionoidea).

Abstract: Coffee berry borer (CBB), Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), is the most serious insect pest of coffee worldwide. Green coffee used in blending and roasting is traded between countries and may be subjected to fumigation for disinfestation of CBB. For example, green coffee shipped to Hawaii from the U.S. mainland must be treated with methyl bromide. Irradiation is an alternative disinfestation treatment option. Dose-response tests were conducted with adult beetles to identify a sterilizing dose, followed by large-scale confirmatory tests with adults infesting coffee berries at 100 Gy (measured doses 84-102 Gy). In total, 6,598 adult CBBs naturally infesting dried coffee berries were irradiated at 100 Gy and produced no viable offspring, whereas 1,033 unirradiated controls produced 327 eggs, 411 larvae, and 58 pupae at 3 wk post treatment. This is the first study to develop a postharvest irradiation treatment for a scolytine bark beetle and supports other studies suggesting 150 Gy is sufficient to prevent reproduction in snout beetles in the superfamily Curculionoidea.

coffee berry borer
Curculionoidea
phytosanitary irradiation
quarantine pest
x-ray


Anti-fungal bandages containing cinnamon extract.

Abstract: Cinnamon-containing polycaprolactone (PCL) bandages were produced by pressurised gyration and their anti-fungal activities against Candida albicans were investigated. It was found that by preparing and spinning polymer solutions of cinnamon with PCL, fibres capable of inhibiting fungal growth could be produced, as observed in disk diffusion tests for anti-fungal susceptibility. Fascinatingly, compared with raw cinnamon powder, the novel cinnamon-loaded fibres had outstanding long-term activity. The results presented here are very promising and may indeed accelerate a new era of using completely natural materials in biomedical applications, especially in wound healing.

Ahmed|Jubair|J|
Altun|Esra|E|
Aydogdu|Mehmet O|MO|
Gunduz|Oguzhan|O|
Kerai|Laxmi|L|
Ren|Guogang|G|
Edirisinghe|Mohan|M|

D000935:Antifungal Agents
D001458:Bandages
D002176:Candida albicans
D002935:Cinnamomum zeylanicum
D010936:Plant Extracts
D011091:Polyesters

anti-fungal
bandages
Cinnamon
healthcare
mass production