Shielding Parenteral Nutrition Solutions From Light: A Randomized Controlled Trial.

Abstract:
INTRODUCTION
Oxidant stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Light induces peroxide generation in parenteral nutrition (PN) solutions, creating an oxidant stress. Shielding PN from light decreases its peroxide content, which has nutrition and biochemical benefits in animals and humans. This study aims at determining whether full light protection of PN decreases the rate of bronchopulmonary dysplasia and/or death in very low-birth-weight infants.

METHODS
Multicenter randomized controlled trial of photoprotection, using amber bags and tubing initiated during compounding of PN and maintained throughout infusion in the light-protected (LP) group. The control group (light exposed [LE]) received PN exposed to ambient light. Depending on centers, lipids were infused either separately or as all-in-one PN.

RESULTS
In total, 590 infants born <30 weeks gestational age were included. At randomization, LE and LP groups did not differ clinically except for maximal FiO2 before 12 hours. The rate of BPD/death was not different between groups at 28 days (77% LP vs 72% LE, P = .16) or at 36 weeks corrected age (30% LP vs 27% LE, P = .55). Multivariate analysis showed no significant effect of photoprotection on BPD and/or death. The rate of BPD/death was significantly lower (odds ratio, 0.54; 95% confidence interval, 0.32-0.93; P = .02) in infants receiving all-in-one PN vs those who received lipids separately.

CONCLUSION
This study did not show significant beneficial effects of photoprotection. Since the decreased rate of BPD/death found with all-in-one PN relates to a center-dependent variable, this warrants further investigation.

Laborie|Sophie|S| Denis|Angélique|A| Dassieu|Gilles|G| Bedu|Antoine|A| Tourneux|Pierre|P| Pinquier|Didier|D| Kermorvant|Elsa|E| Millet|Véronique|V| Klosowski|Serge|S| Patural|Hugues|H| Clamadieu|Catherine|C| Brunhes|Anne|A| Walther|Marie|M| Jaisson-Hot|Isabelle|I| Mandy|Bruno|B| Claris|Olivier|O|

D001997:Bronchopulmonary Dysplasia
D005260:Female
D006801:Humans
D007231:Infant, Newborn
D019102:Infant, Very Low Birth Weight
D007363:Intensive Care Units, Neonatal
D008027:Light
D008297:Male
D015999:Multivariate Analysis
D018384:Oxidative Stress
D057947:Parenteral Nutrition Solutions
D010545:Peroxides
D011446:Prospective Studies
D011835:Radiation Protection
D016896:Treatment Outcome

parenteral nutrition
bronchopulmonary dysplasia
peroxides
preterm infant
very low birth weight


Heterogeneous production of proteases from Brazilian clinical isolates of Pseudomonas aeruginosa.

Abstract:
BACKGROUND
Pseudomonas aeruginosa is an important human pathogen that causes severe infections in a wide range of immunosuppressed patients. Herein, we evaluated the proteolytic profiles of 96 Brazilian clinical isolates of P. aeruginosa recovered from diverse anatomical sites.

METHODS
Cell-associated and extracellular proteases were evidenced by gelatin-SDS-PAGE and by the cleavage of soluble gelatin. Elastase was measured by using the peptide substrate N-succinyl-Ala-Ala-Ala-p-nitroanilide. The prevalence of elastase genes (lasA and lasB) was evaluated by PCR.

RESULTS
Bacterial extracts were initially applied on gelatin-SDS-PAGE and the results revealed four distinct zymographic profiles as follows: profile I (composed by bands of 145, 118 and 50kDa), profile II (118 and 50kDa), profile III (145kDa) and profile IV (118kDa). All the proteolytic enzymes were inhibited by EDTA, identifying them as metalloproteases. The profile I was the most detected in both cellular (79.2%) and extracellular (84.4%) extracts. Overall, gelatinase and elastase activities measured in the spent culture media were significantly higher (around 2-fold) compared to the cellular extracts and the production level varied according to the site of bacterial isolation. For instance, tracheal secretion isolates produced elevated amount of gelatinase and elastase measured in both cellular and extracellular extracts. The prevalence of elastase genes revealed that 100% isolates were lasB-positive and 85.42% lasA-positive. Some positive/negative correlations were showed concerning the production of gelatinase, elastase, isolation site and antimicrobial susceptibility.

CONCLUSION
The protease production was highly heterogeneous in Brazilian clinical isolates of P. aeruginosa, which corroborates the genomic/metabolic versatility of this pathogen.

Galdino|Anna Clara M|ACM|
Viganor|Lívia|L|
Ziccardi|Mariangela|M|
Nunes|Ana Paula F|APF|
Dos Santos|Kátia R N|KRN|
Branquinha|Marta H|MH|
Santos|André L S|ALS|

Proteases
Brazilian clinical isolates
Pseudomonas aeruginosa
Elastase
Gelatinases
Aislamientos clínicos brasileños
Elastasa
Factores virulentos
Gelatinasas
Proteasas
Virulence factors


Preventive effects of astragaloside IV and its active sapogenin cycloastragenol on cardiac fibrosis of mice by inhibiting the NLRP3 inflammasome.

Abstract: Cardiac fibrosis is a common feature of many cardiac pathophysiologic conditions. Recently, it has been shown that the activation of NLRP3 inflammasome plays an important role in the pathophysiology of cardiac fibrosis. Here, the inhibitory effects and possible mechanism of astragaloside IV (AST) and its active sapogenin cycloastragenol (CAG) on isoproterenol (ISO)-induced cardiac fibrosis were investigated. In our study, BALB/c mice were subcutaneously injected with 5 mg/kg ISO for 7 consecutive days to induce cardiac fibrosis. AST or CAG was administrated to the mice intragastrically at different doses beginning on the same day of ISO injection. Primary cardiac fibroblasts were isolated from the hearts of neonatal rats, and treated with 10 μmol/L ISO for 24 h with or without incubation of CAG simultaneously. The results indicated that 62.5 mg/kg CAG could significantly inhibit ISO-induced cardiac fibrosis, which was evidenced by sirius red staining, collagen volume fraction and mRNA expressions of collagen-1, collagen-3 and TGF-β1. Hematoxylin-eosin staining showed that 62.5 mg/kg CAG markedly reduced the inflammatory cell infiltration in heart tissues. To elucidate the related mechanism, NLRP3/caspase-1/IL-18 pathway was studied. The mRNA expressions of NLRP3, caspase-1, IL-18 and IL-6 in mice heart tissues were significantly down-regulated by 62.5 mg/kg CAG and 200 mg/kg AST. And incubation with 31.25 μg/ml CAG markedly attenuated ISO-induced mRNA over-expressions of NLRP3, caspase-1, IL-18 and IL-6 in primary cardiac fibroblasts. These findings showed that CAG effectively inhibited ISO-induced cardiac fibrosis, and both CAG and AST exhibited anti-fibrosis effects through inhibition of the NLRP3 inflammasome pathway.

Wan|Yu|Y| Xu|Lu|L| Wang|Yunxia|Y| Tuerdi|Nuerbiya|N| Ye|Min|M| Qi|Rong|R|

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein

Astragaloside IV
Cycloastragenol
Cardiac fibrosis
NLRP3 inflammasome


TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology.

Abstract: Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of TMA were proposed several decades ago. We assessed plasma TMA and TMAO levels in healthy humans (HH) and cardiovascular patients qualified for aortic valve replacement (CP). The cytotoxicity of TMA and TMAO in rat cardiomyocytes was evaluated using an MTT test. The effects of TMA and TMAO on albumin and lactate dehydrogenase (LDH) were assessed using fluorescence correlation spectroscopy. In comparison to HH, CP had a two-fold higher plasma TMA (p < 0.001) and a trend towards higher plasma TMAO (p = 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR, p = 0.002). TMA but not TMAO reduced cardiomyocytes viability. Incubation with TMA but not TMAO resulted in the degradation of the protein structure of LDH and albumin. In conclusion, CP show increased plasma TMA, which is inversely correlated with eGFR. TMA but not TMAO exerts negative effects on cardiomyocytes, likely due to its disturbing effect on proteins. Therefore, TMA but not TMAO may be a toxin and a marker of cardiovascular risk.

TMAO
trimethylamine
bacterial metabolites
biomarkers


Serum cholinesterase biomarker study in farmers - Souss Massa region-, Morocco: case-control study.

Abstract: Background: Farmers and their workers are exposed to a wide variety of pesticides. The use of pesticides has been documented to lead to several adverse health effects. Inhibition of cholinesterase, primarily butyrylcholinesterase is a good indicator of occupational exposure to organophosphates and carbamates.Objective: This case-control study aims to study the risks associated with pesticide exposure among farmers and agricultural workers in the Souss Massa region by analyzing variations in the response of a pesticides exposure biomarker: Serum Cholinesterase Activity (butyrylcholinesterase (BChE)).Materials and methods: This was a prospective study conducted on 133 participants (71 farmers and 62 non-farmers). A structured questionnaire was applied collecting socio-demographic information and determining knowledge and work practices in relation to pesticide use. The activity of Serum cholinesterase was measured by the butyrulthiocholine method a spectrophotometric assay.Results: The mean age of the participants was 42.5 ± 10.66 years. The study demonstrated significantly lower BChE activity, respectively, in the plasma of farmers exposed to pesticides, compared to the control group (p < 0.05). The measured mean level of BChE activity was (7304.80 ± 1939.99 U/L) and (9746.42 ± 1699.85 U/L) in the farmers and the control group (non-farmers), respectively. In addition, a high proportion of farmers reported that empty containers are burned in the open (74.6%) for waste disposal. A proportion (11.3%) of farmers also reported that empty container waste is spilled on the farm.Conclusions: The decrease in BChE indicates a serious public health problem among farmers who use organophosphate pesticides. This study suggests that regular monitoring for blood cholinesterase and effective interventions to reduce pesticide exposure to prevent health effects should be provided to farmers.

Serum cholinesterase
biomarker
farmers
morocco
pesticide


Nonoperative Ablation of Pancreatic Neoplasms.

Abstract: Pancreatic cancer is a poor prognostic tumor and about 20% of patients are eligible for surgical resection at the time of diagnosis. Recently, minimally invasive procedures have provided promising results as a therapeutic option for locally advanced unresectable pancreatic cancer. In particular, high-intensity focused ultrasound is an emerging noninvasive thermally ablative procedure that may have a dominant role in the future. Although the clinical applications of minimally invasive therapies to pancreatic cancers are still in their infancy, the results at present are promising.

Marrocchio|Cristina|C| Dababou|Susan|S| Catalano|Carlo|C| Napoli|Alessandro|A|

D019060:Minimally Invasive Surgical Procedures

Pancreatic cancer
High-intensity focused ultrasound
Minimally invasive therapies
Cryotherapy
Irreversible electroporation
Microwave ablation
Radiofrequency ablation


Inhibition of BCR signaling using the Syk inhibitor TAK-659 prevents stroma-mediated signaling in chronic lymphocytic leukemia cells.

Abstract: Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment. To ex vivo mimic the microenvironment found in the proliferation centers, we co-cultured primary CLL cells with BM stromal cells (BMSC), CD40L and CpG ODN along with BCR stimulation. In this setting, TAK-659 inhibited the microenvironment-induced activation of Syk and downstream signaling molecules, without inhibiting the protein homologue ZAP-70 in T cells. Importantly, the pro-survival, proliferative, chemoresistant and activation effects promoted by the microenvironment were abrogated by TAK-659, which furthermore blocked CLL cell migration toward BMSC, CXCL12, and CXCL13. Combination of TAK-659 with other BCR inhibitors showed synergistic effect in inducing apoptosis, and the sequential addition of TAK-659 in ibrutinib-treated CLL cells induced significantly higher cytotoxicity. These findings provide a strong rationale for the clinical development of TAK-659 in CLL.

Purroy|Noelia|N| Carabia|Júlia|J| Abrisqueta|Pau|P| Egia|Leire|L| Aguiló|Meritxell|M| Carpio|Cecilia|C| Palacio|Carles|C| Crespo|Marta|M| Bosch|Francesc|F|

D015451:Leukemia, Lymphocytic, Chronic, B-Cell

Syk
TAK-659
CLL
microenvironment
BCR inhibitor


Novel Clinical Risk Scoring Model for Predicting Amputation in Patients With Necrotizing Fasciitis: The ANF Risk Scoring System.

Abstract: Background: Necrotizing fasciitis (NF) is a life-threatening infection of the skin and soft tissue that spreads quickly and requires immediate surgery and medical treatment. Amputation or radical debridement of necrotic tissue is generally always required. The risks and benefits of both the surgical options are weighed before deciding whether to amputate or debride. This study set forth to create an easy-to-use risk scoring system for predicting the risk scoring system for amputation in patients with NF (ANF). Methods: This retrospective study included 1,506 patients diagnosed with surgically confirmed NF at three general hospitals in Thailand from January 2009 to December 2012. All diagnoses were made by surgeons who strictly observed the guidelines for skin and soft tissue infections produced by the Infectious Diseases Society of America. Patients were randomly allocated to either the derivation (n = 1,193) or validation (n = 313) cohort. Clinical risk factors assessed at the time of recruitment were used to create the risk score, which was then developed using logistic regression. The regression coefficients were converted into item scores, and the total score was calculated. Results: The following four clinical predictors were used to create the model: female gender, diabetes mellitus, wound appearance stage 3 (skin necrosis and gangrene), and creatinine ≥1.6 mg/dL. Using the area under the receiver operating characteristic curve (AuROC), the ANF system showed moderate power (78.68%) to predict amputation in patients with NF with excellent calibration (Hosmer-Lemeshow χ2 = 2.59; p = 0.8586). The positive likelihood ratio of amputation in low-risk (score ≤ 4) and high-risk (score ≥ 7) patients was 2.17 (95%CI: 1.66-2.82) and 6.18 (95%CI: 4.08-9.36), respectively. The ANF system showed good performance (AuROC 76.82%) when applied in the validation cohort. Conclusion: The developed ANF risk scoring system, which includes four easy to obtain predictors, provides physicians with prediction indices for amputation in patients with NF. This model will assist clinicians with surgical decision-making in this time-sensitive clinical setting.

Chaomuang|Natthaya|N| Khamnuan|Patcharin|P| Chuayunan|Nipaporn|N| Duangjai|Acharaporn|A| Saokaew|Surasak|S| Phisalprapa|Pochamana|P|

clinical risk scoring model
amputation
patients
necrotizing fasciitis
ANF risk scoring system


A Mobile Phone-Based Program to Promote Healthy Behaviors Among Adults With Prediabetes Who Declined Participation in Free Diabetes Prevention Programs: Mixed-Methods Pilot Randomized Controlled Trial.

Abstract:
BACKGROUND
Despite evidence that Diabetes Prevention Programs (DPPs) can delay or prevent progression to type 2 diabetes mellitus (T2DM), few individuals with prediabetes enroll in offered programs. This may be in part because many individuals with prediabetes have low levels of autonomous motivation (ie, motivation that arises from internal sources) to prevent T2DM.

OBJECTIVE
This study aims to examine the feasibility and acceptability of a mobile health (mHealth) intervention designed to increase autonomous motivation and healthy behaviors among adults with prediabetes who previously declined participation free DPPs. In addition, the study aims to examine changes in autonomous motivation among adults offered 2 versions of the mHealth program compared with an information-only control group.

METHODS
In this 12-week, parallel, 3-arm, mixed-methods pilot randomized controlled trial, participants were randomized to (1) a group that received information about prediabetes and strategies to prevent T2DM (control); (2) a group that received a mHealth app that aims to increase autonomous motivation among users (app-only); or (3) a group that received the app plus a physical activity tracker and wireless-enabled digital scale for self-monitoring (app-plus). Primary outcome measures included rates of intervention uptake (number of individuals enrolled/number of individuals assessed for eligibility), retention (number of 12-week survey completers/number of participants), and adherence (number of device-usage days). The secondary outcome measure was change in autonomous motivation (measured using the Treatment Self-Regulation Questionnaire), which was examined using difference-in-difference analysis. Furthermore, we conducted postintervention qualitative interviews with participants.

RESULTS
Overall, 28% (69/244) of eligible individuals were randomized; of these, 80% (55/69) completed the 12-week survey. Retention rates were significantly higher among app-plus participants than participants in the other 2 study arms combined (P=.004, χ2). No significant differences were observed in adherence rates between app-only and app-plus participants (43 days vs 37 days; P=.34). Among all participants, mean autonomous motivation measures were relatively high at baseline (6.0 of 7.0 scale), with no statistically significant within- or between-group differences in follow-up scores. In qualitative interviews (n=15), participants identified reasons that they enjoyed using the app (eg, encouraged self-reflection), reasons that they did not enjoy using the app (eg, did not consider personal circumstances), and strategies to improve the intervention (eg, increased interpersonal contact).

CONCLUSIONS
Among individuals with prediabetes who did not engage in free DPPs, this mHealth intervention was feasible and acceptable. Future work should (1) examine the effectiveness of a refined intervention on clinically relevant outcomes (eg, weight loss) among a larger population of DPP nonenrollees with low baseline autonomous motivation and (2) identify other factors associated with DPP nonenrollment, which may serve as additional potential targets for interventions.

TRIAL REGISTRATION
ClinicalTrials.gov NCT03025607; https://clinicaltrials.gov/ct2/show/NCT03025607 (Archived by WebCite at http://www.webcitation.org/73cvaSAie).

prediabetes
prevention
type 2 diabetes mellitus
autonomous motivation
mHealth
behavioral change
mobile phone


Predictors of chronic ankle instability after an index lateral ankle sprain: a systematic review.

Abstract:
OBJECTIVES
To identify the predictors of chronic ankle instability after an index lateral ankle sprain.

DESIGN
Systematic review.

METHODS
The databases of MEDLINE, CINAHL, AMED, Scopus, SPORTDiscus, Embase, Web of Science, PubMed, PEDro, and Cochrane Register of Clinical Trials were searched from the earliest record until May 2013. Prospective studies investigating any potential intrinsic predictors of chronic ankle instability after an index ankle sprain were included. Eligible studies had a prospective design (follow-up of at least three months), participants of any age with an index ankle sprain, and had assessed ongoing impairments associated with chronic ankle instability. Eligible studies were screened and data extracted by two independent reviewers.

RESULTS
Four studies were included. Three potential predictors of chronic ankle instability, i.e., postural control, perceived instability, and severity of the index sprain, were investigated. Decreased postural control measured by number of foot lifts during single-leg stance with eyes closed and perceived instability measured by Cumberland Ankle Instability Tool were not predictors of chronic ankle instability. While the results of one study showed that the severity of the initial sprain was a predictor of re-sprain, another study did not.

CONCLUSIONS
Of the three investigated potential predictors of chronic ankle instability after an index ankle sprain, only severity of initial sprain (grade II) predicted re-sprain. However, concerns about validity of the grading system suggest that these findings should be interpreted with caution.

Pourkazemi|Fereshteh|F|
Hiller|Claire E|CE|
Raymond|Jacqueline|J|
Nightingale|Elizabeth J|EJ|
Refshauge|Kathryn M|KM|

D016512:Ankle Injuries
D002908:Chronic Disease
D015444:Exercise
D006801:Humans
D007593:Joint Instability
D004856:Postural Balance

Ankle sprains
Joint instability
Postural balance
Sprain severity


Development of phenotypic screening assays for γ-globin induction using primary human bone marrow day 7 erythroid progenitor cells.

Abstract: Sickle cell anemia (SCA) is a genetic disorder of the β-globin gene. SCA results in chronic ischemia with pain and tissue injury. The extent of SCA symptoms can be ameliorated by treatment with drugs, which result in increasing the levels of γ-globin in patient red blood cells. Hydroxyurea (HU) is a Food and Drug Administration-approved drug for SCA, but it has dose-limiting toxicity, and patients exhibit highly variable treatment responses. To identify compounds that may lead to the development of better and safer medicines, we have established a method using primary human bone marrow day 7 erythroid progenitor cells (EPCs) to screen for compounds that induce γ-globin production. First, human marrow CD34(+) cells were cultured and expanded for 7 days and characterized for the expression of erythroid differentiation markers (CD71, CD36, and CD235a). Second, fresh or cryopreserved EPCs were treated with compounds for 3 days in 384-well plates followed by γ-globin quantification by an enzyme-linked immunosorbent assay (ELISA), which was validated using HU and decitabine. From the 7408 compounds screened, we identified at least one new compound with confirmed γ-globin-inducing activity. Hits are undergoing analysis in secondary assays. In this article, we describe the method of generating fit-for-purpose EPCs; the development, optimization, and validation of the ELISA and secondary assays for γ-globin detection; and screening results.

Li|Hu|H|
Xie|Wensheng|W|
Gore|Elizabeth R|ER|
Montoute|Monica N|MN|
Bee|Weilin Tiger|WT|
Zappacosta|Francesca|F|
Zeng|Xin|X|
Wu|Zining|Z|
Kallal|Lorena|L|
Ames|Robert S|RS|
Pope|Andrew J|AJ|
Benowitz|Andrew|A|
Erickson-Miller|Connie L|CL|

phenotypic screen
γ-globin
sickle cell anemia
hydroxyurea (HU)
ELISA
decitabine
fetal hemoglobin (HbF)


Re2O7-catalyzed formal [3 + 2] cycloaddition for diverse naphtho[1,2-b]furan-3-carboxamides and their biological evaluation.

Abstract: Diverse naphtho[1,2-b]furan-3-carboxamide derivatives 12a-12q were synthesized in high yield via the novel Re2O7-catalyzed formal [3 + 2] cycloaddition of 1,4-naphthoquinones with β-ketoamides as the key step. This methodology offers several advantages, such as environmentally benign character, the use of a mild catalyst, high yields, and ease of handling. The synthesized compounds were screened for their tyrosinase inhibitory, antioxidant, and antibacterial activities. The results showed that compound 12c exhibited excellent tyrosinase inhibitory activity with an IC50 of 13.48 μg/mL, which is comparable to that of kojic acid (IC50 = 19.45 μg/mL). Compounds 12a, 12b, and 12i displayed moderate antioxidant activities in a DPPH assay. Compound 12m showed good activity against S. aureus (MIC = 16 μg/mL), and compound 12p was found to be active against E. coli (MIC = 16 μg/mL).

Xia|Likai|L|
Idhayadhulla|Akber|A|
Lee|Yong Rok|YR|

D000900:Anti-Bacterial Agents
D018360:Crystallography, X-Ray
D061565:Cycloaddition Reaction
D004926:Escherichia coli
D005663:Furans
D008826:Microbial Sensitivity Tests
D015394:Molecular Structure
D009281:Naphthalenes
D012211:Rhenium
D013211:Staphylococcus aureus

Cycloaddition
Antioxidant
Antibacterial activity
Anti-tyrosinase
Naphtho[1, 2-b]furan-3-carboxamides


Residual limb claudication after vascular transfemoral amputation.

Abstract:
BACKGROUND
In all, 68% of all lower limb amputees experience residual limb pain. More than 95% of all lower limb amputations in developed countries are due to peripheral artery occlusive disease in combination with diabetes mellitus. Therefore, claudication, which is one of the most common manifestations of peripheral artery occlusive disease, should be taken into consideration in making a differential diagnosis of residual limb pain. Case description and methods: We present a case study of a 60-year-old diabetic patient who underwent a transfemoral amputation due to peripheral artery occlusive disease and who experiences residual limb pain. A computed tomography angiography was performed, and we searched for relevant literature on claudication pain after lower limb amputation.

CONCLUSION
Little research has explored claudication as a cause of residual limb pain. More research will lead to a decrease in unnecessary prosthetic fittings and adjustments give more insight into the treatment and management of residual limb pain and prevent a decrease in mobility in amputees. Clinical relevance Claudication due to peripheral artery occlusive disease should be included as a possible cause of residual limb pain to prevent unnecessary prosthetic fittings and adjustments and to minimize psychological effects and limitations in activities and participation.

de Boer|Riemke Ga|RG|
Paping|Marieke A|MA|
Kap|Bert|B|
Geertzen|Jan Hb|JH|

claudication
residual limb pain
Lower limb amputation
peripheral artery occlusive disease


Interests and concerns of the Army Medical Services as reflected by the publications in the Journal of the Royal Army Medical Corps 1903-2019.

Abstract:
INTRODUCTION
The Journal of the Royal Army Medical Corps (JRAMC) is published with the aim of propagating current knowledge and expertise while also acting as institutional memory for the practice of medicine within the military. This work aimed to examine how the interests of the JRAMC, and by inference the Army Medical Services, have changed over time as reflected by the articles published in the journal.

METHODS
A text mining analysis of the titles of all published articles in the JRAMC between 1903 and 2019 was performed. The most commonly used terms were identified and their relative frequency over the decades analysed to identify trends. Article content and contemporary events were compared with the observed trends to identify explanatory events and themes of interest.

RESULTS
Medical topics of interest centred around specific infectious diseases, particularly during the early/mid-20th century, and trauma and battle injury. The medical specialties of surgery, anaesthetics and mental health were all well represented in nearly all decades, while primary care only came to prominence as a named specialty from the 1960s onwards. India, France, Egypt and wider Africa were the most commonly cited geographical regions, although there were spikes of interest associated with specific conflicts in the Falklands, Bosnia, Afghanistan and Iraq.

CONCLUSION
The interests of the JRAMC have changed considerably over the years primarily driven by the geopolitical interests of Britain-in particular its colonial interests and the conflicts it has been involved in, but also by medical advances seen in contemporary society.

Text Mining
Medical History
Military Medical History


Defective repair capacity of variant proteins of the DNA glycosylase NTHL1 for 5-hydroxyuracil, an oxidation product of cytosine.

Abstract: The NTHL1 gene encodes DNA glycosylase, which is involved in base excision repair, and biallelic mutations of this gene result in NTHL1-associated polyposis (NAP), a hereditary disease characterized by colorectal polyposis and multiple types of carcinomas. However, no proper functional characterization of variant NTHL1 proteins has been done so far. Herein, we report functional evaluation of variant NTHL1 proteins to aid in the accurate diagnosis of NAP. First, we investigated whether it would be appropriate to use 5-hydroxyuracil (5OHU), an oxidation product of cytosine, for the evaluation. In the supF forward mutation assay, 5OHU caused an increase of the mutation frequency in human cells, and the C→T mutation was predominant among the 5OHU-induced mutations. In addition, in DNA cleavage activity assay, 5OHU was excised by NTHL1 as well as four other DNA glycosylases (SMUG1, NEIL1, TDG, and UNG2). When human cells overexpressing the five DNA glycosylases were established, it was found that each of the five DNA glycosylases, including NTHL1, had the ability to suppress 5OHU-induced mutations. Based on the above results, we performed functional evaluation of eight NTHL1 variants using 5OHU-containing DNA substrate or shuttle plasmid. The DNA cleavage activity assay showed that the variants of NTHL1, Q90X, Y130X, R153X, and Q287X, but not R19Q, V179I, V217F, or G286S, showed defective repair activity for 5OHU and two other oxidatively damaged bases. Moreover, the supF forward mutation assay showed that the four truncated-type NTHL1 variants showed a reduced ability to suppress 5OHU-induced mutations in human cells. These results suggest that the NTHL1 variants Q90X, Y130X, R153X, and Q287X, but not R19Q, V179I, V217F, or G286S, were defective in 5OHU repair and the alleles encoding them were considered to be pathogenic for NAP.

Shinmura|Kazuya|K| Kato|Hisami|H| Kawanishi|Yuichi|Y| Goto|Masanori|M| Tao|Hong|H| Yoshimura|Katsuhiro|K| Nakamura|Satoki|S| Misawa|Kiyoshi|K| Sugimura|Haruhiko|H|

DNA glycosylase
NTHL1
5-hydroxyuracil
NTHL1-associated polyposis
supF forward mutation assay
C→T mutation
DNA cleavage activity assay


Sex differences in the shared genetics of dimensions of self-reported depression and anxiety.

Abstract:
BACKGROUND
The prevalence of depression and anxiety symptoms and their comorbidity varies between males and females for reasons still unknown. This study aims to test whether differences between males and females in self-reported symptoms and their covariation are caused by variations in the magnitude of genetic and environmental factors.

METHODS
750 monozygotic and dizygotic healthy twin pairs (18-60 years; M=39.77 years) participated in the TWIN-E project. Univariate and multivariate genetic modelling was undertaken using the Depression Anxiety Stress Scale (DASS-42).

RESULTS
Additive genetics and unique environment contributed to self-reported depression (heritability, h(2): 34%), anxiety (h(2): 30%) and stress (h(2): 34%) scores in univariate models, and to the common latent factor (h(2): 39%) in the multivariate model. No sex differences in magnitude of estimates for DASS-42 scores were found in the univariate model. However when considering correlated depression and anxiety symptomatology only shared genetic factors between depression and anxiety contributed to depression scores in males, but both specific and shared genetic factors contributed to depression scores in females.

LIMITATIONS
The results are limited to the sample of healthy, community, adult, same sex twin pairs who participated in the study.

CONCLUSIONS
Differences in males and females in genetic aetiology of self-reported dimensions of depression are only apparent when taking into consideration the covariation with self-reported anxiety. This difference is highlighted by the finding that both common and specific genetic factors contribute to self-reported depression in females but not males. This novel finding may help explain the increased incidence of depression symptoms in females.

Burton|Karen L O|KL|
Williams|Leanne M|LM|
Richard Clark|C|C|
Harris|Anthony|A|
Schofield|Peter R|PR|
Gatt|Justine M|JM|

Depression Anxiety Twin Multivariate Stress Heritability


Insights on supporting the aging brain microvascular endothelium.

Abstract: Blood brain barrier hyperpermeability has been associated with age-related affective disorders, including depression, mania, anxiety, Alzheimer's and Parkinson's disease. Our recent efforts suggest that a promising therapeutic approach may arise due to the activation of the unfolded protein response (UPR) element in the affected tissues. Growth hormone releasing hormone antagonists and heat shock protein 90 inhibitors have been shown to induce UPR. This mechanism (UPR) has been associated with tissue repairing processes.

Blood brain barrier
Unfolded protein response
Growth hormone releasing hormone
P53
Reactive oxygen species


Nuclear Receptor Nr4a1 Regulates Striatal Striosome Development and Dopamine D1 Receptor Signaling.

Abstract: The GABAergic medium-size spiny neuron (MSN), the striatal output neuron, may be classified into striosome, also known as patch, and matrix, based on neurochemical differences between the two compartments. At this time, little is known regarding the regulation of the development of the two compartments. Nr4a1, primarily described as a nuclear receptor/immediate early gene involved in the homeostasis of the dopaminergic system, is a striosomal marker. Using Nr4a1-overexpressing and Nr4a1-null mice, we sought to determine whether Nr4a1 is necessary and/or sufficient for striosome development. We report that in vivo and in vitro, Nr4a1 and Oprm1 mRNA levels are correlated. In the absence of Nr4a, there is a decrease in the percentage of striatal surface area occupied by striosomes. Alterations in Nr4a1 expression leads to dysregulation of multiple mRNAs of members of the dopamine receptor D1 signal transduction system. Constitutive overexpression of Nr4a1 decreases both the induction of phosphorylation of ERK after a single cocaine exposure and locomotor sensitization following chronic cocaine exposure. Nr4a1 overexpression increases MSN excitability but reduces MSN long-term potentiation. In the resting state, type 5 adenylyl cyclase (AC5) activity is normal, but the ability of AC5 to be activated by Drd1 G-protein-coupled receptor inputs is decreased. Our results support a role for Nr4a1 in determination of striatal patch/matrix structure and in regulation of dopaminoceptive neuronal function.

D057105:Nuclear Receptor Subfamily 4, Group A, Member 1

Nr4a1
striosome
signal
dopamine receptor D1
transduction
ERK


Intra-aortic balloon pump in coronary artery bypass graft - factors affecting outcome.

Abstract:
BACKGROUND
The management of coronary artery bypass graft (CABG) patients, especially in high risk patients ,can be challenging as the postoperative periods may be characterized by a low cardiac output state. Inotropes used in the perioperative periods to increase cardiac output may be detrimental thus making the use of mechanical devices like intra-aortic Balloon pump (IABP) for circulatory assistance desirable.

AIMS & OBJECTIVES
To study the use of intra-aortic balloon pump in coronary artery bypass patients in preoperative and post operative settings and factors that affect morbidity and mortality.

SETTING
Madras Medical Mission, Chennai, India.

METHOD
A retrospective study of 3974 consecutive patients who had CABG done between March 2007 and February 2011 with or without additional procedures. One hundred and seven (2.7%) patients had IABP instituted either pre-operatively or postoperatively when it was obvious the patient will need cardiac assistance. The demographic data, clinical features, the indications for insertion, management offered and outcome , the creatinine levels, the duration of intraarortic balloon pump, the intensive care unit(ICU) and Hospital stay were analyzed for means and standard deviations and Pearsons Chi-square test using SPSS 10.0 window soft ware version with significant value of p-value<0.005.

RESULT
The mean age of all the patients was 59.7 + SD 10.7, 85(79.4%) patients were males,22(20.6%) were females .Out of the 107 patient who had IABP insertion, 59(55.1%) patients had IABP inserted preoperatively and 48(44.9%) postoperatively. The creatinine levels after the insertion of IABP in 68 patients was<1.5mg/dl and in 39 patients was>1.5mg/dl with mortality of 15.0% for the preoperative insertion group versus 29.0% for the postoperative group respectively (p=0.005). The preoperative and postoperative insertion ICU stay were 8.3+4.7 days and 5.7+1.6days respectively (p=0.005) and mortality were16.8% and 27.1 %( p=0.005) respectively.

CONCLUSION
Early institution of intra-aortic balloon pump gives a better outcome even in high risk coronary artery bypass graft patients as it reduces ICU stay and mortality, and elevated post-insertion creatinine levels has been shown to be an indicator of impending mortality and so an early warning for putting in place mitigating protocols.

Intra-aortic balloon pump
Coronary artery bypass graft
Creatinine levels
Low Cardiac Output Syndrome
Maximum inotropic dose


Back to Acid Soil Fields: The Citrate Transporter SbMATE Is a Major Asset for Sustainable Grain Yield for Sorghum Cultivated on Acid Soils.

Abstract: Aluminum (Al) toxicity damages plant roots and limits crop production on acid soils, which comprise up to 50% of the world's arable lands. A major Al tolerance locus on chromosome 3, AltSB, controls aluminum tolerance in sorghum [Sorghum bicolor (L.) Moench] via SbMATE, an Al-activated plasma membrane transporter that mediates Al exclusion from sensitive regions in the root apex. As is the case with other known Al tolerance genes, SbMATE was cloned based on studies conducted under controlled environmental conditions, in nutrient solution. Therefore, its impact on grain yield on acid soils remains undetermined. To determine the real world impact of SbMATE, multi-trait quantitative trait loci (QTL) mapping in hydroponics, and, in the field, revealed a large-effect QTL colocalized with the Al tolerance locus AltSB, where SbMATE lies, conferring a 0.6 ton ha(-1) grain yield increase on acid soils. A second QTL for Al tolerance in hydroponics, where the positive allele was also donated by the Al tolerant parent, SC283, was found on chromosome 9, indicating the presence of distinct Al tolerance genes in the sorghum genome, or genes acting in the SbMATE pathway leading to Al-activated citrate release. There was no yield penalty for AltSB, consistent with the highly localized Al regulated SbMATE expression in the root tip, and Al-dependent transport activity. A female effect of 0.5 ton ha(-1) independently demonstrated the effectiveness of AltSB in hybrids. Al tolerance conferred by AltSB is thus an indispensable asset for sorghum production and food security on acid soils, many of which are located in developing countries.

Carvalho|Geraldo|G|
Schaffert|Robert Eugene|RE|
Malosetti|Marcos|M|
Viana|Joao Herbert Moreira|JH|
Menezes|Cicero Bezerra|CB|
Silva|Lidianne Assis|LA|
Guimaraes|Claudia Teixeira|CT|
Coelho|Antonio Marcos|AM|
Kochian|Leon V|LV|
van Eeuwijk|Fred A|FA|
Magalhaes|Jurandir Vieira|JV|

Al tolerance
AltSB
Sorghum bicolor
QTL mapping
field trials


Pathophysiological mechanisms of gonadotropins- and steroid hormones-related genes in etiology of polycystic ovary syndrome.

Abstract:
Objectives
Polycystic ovary syndrome (PCOS) is an endocrinopathy in women, which, unlike its impact on fertility and health of women, there is no clear understanding about the causal mechanisms of this pathogenesis. The aim of this review paper is to investigate the pathophysiological pathways affecting the PCOS etiology, based on functions of gonadotropins- and steroid hormones-related genes.

Materials and Methods
Due to different hormonal and metabolic signs of this complex disorder, different hypotheses are mentioned about etiology of this syndrome. Because of the heterogeneity of the reasons given for this syndrome and the spread of the effective genes in its pathophysiology, most of genes affected by sex-related hormonal imbalances are examined for discriminative diagnosis. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review.

Results
In previous studies, it has been well demonstrated that PCOS in some individuals have a genetic origin. Pathophysiological functions of genes are primarily responsible for the synthesis of proteins that have role in PCOS before hyperandrogenism including GnRHR, FSHβ, FSHR, LHCGR, CYP19A1, HSD17B, AR and SHBG, and their effects in PCOS of human have been confirmed.

Conclusion
Hormonal imbalances are the first reason mentioned in PCOS etiology, and usually characterized with menstrual irregularities in PCOS women. Hyperandrogenism and gonadotropin secretion disorders are shown in PCOS condition, which are related to steroidogenesis pathways and hypothalamic-pituitary-ovarian axis disturbances, respectively.

Shaaban|Zahra|Z|
Khoradmehr|Arezoo|A|
Jafarzadeh Shirazi|Mohammad Reza|MR|
Tamadon|Amin|A|

Steroids
Genes
Polycystic ovary syndrome
Hormones
Hyperandrogenism
Gonadotropins
Physiopathology


A new nonparametric test for the race model inequality.

Abstract: The race model inequality (RMI), as first introduced by Miller (Cognitive Psychology, 14, 247-279, 1982), entails an upper bound on the amount of statistical facilitation for reaction times (RTs) attainable by a race model within the redundant-signals paradigm. A violation of RMI may be considered as empirical evidence for a coactivation model rather than a race model. Here, we introduce a novel nonparametric procedure for evaluating the RMI for single participant analysis. The statistical procedure is based on a new probabilistic representation that highlights some neglected, but important distributional features of the RMI. In particular, we show how the reconstructed distribution function under maximal statistical facilitation for a race model is characterized by a specific truncated-type property. The results of two Monte Carlo simulation studies suggest that our procedure efficiently controls for type I error with reasonable power. Finally, unlike previous proposals for single participant analysis (e.g., Maris and Maris (Journal of Mathematical Psychology 47, 507-514, 2003)), our approach is also more consistent with the typical way to collect RT data in experimental works. R script functions for running the statistical analysis on single participant data are made freely available to the readers on a dedicated web server.

D006801:Humans
D008960:Models, Psychological
D011930:Reaction Time
D012959:Socioeconomic Factors

Race model inequality
Redundant-signals paradigm
Truncated Kolmogorov–Smirnov test


Top Ten Tips Palliative Care Clinicians Should Know About Caring for Muslims.

Abstract: Islam is the fastest-growing religion across the world and in the United States. Adherents of Islam are known as Muslims. Globally, Muslims comprise the second largest religious group with 1.8 billion people, or 24% of the world's population, and range in racial and ethnic diversity.1 As this population continues to grow, palliative care clinicians will invariably care for a Muslim patient therefore making it important to have a basic understanding of values, traditions, and beliefs held by them. This article outlines 10 basic principles held by many Muslim patients and their families that can allow for palliative care to be delivered in a culturally inclusive way. This article should serve as a point of initiation for further exploration of their needs as it is not a comprehensive guide.

Madni|Arshia|A|
Khan|Shan|S|
Bilbeisi|Tharwa|T|
Pasli|Melisa|M|
Sakaan|Firas|F|
Lahaj|Sister Mary|SM|
Patel|Rushil|R|
Kamal|Arif H|AH|

palliative care
Muslim
Islam
Qur'an
spirituality


pH-Sensitive Chitosan-Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells.

Abstract: Chitosan has been extensively studied as a genetic drug delivery platform. However, its efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding strength of cargo with chitosan, we proposed including heparin as a competing polyanion in the polyplexes. We developed chitosan-heparin nanoparticles by a one-step process for the local delivery of oligonucleotides. The size of the polyplexes was dependent on the mass ratio of polycation to polyanion. The mechanism of oligonucleotide release was pH-dependent and associated with polyplex swelling and collapse of the polysaccharide network. Inclusion of heparin enhanced the oligonucleotide release from the chitosan-based polyplexes. Furthermore, heparin reduced the toxicity of polyplexes in the cultured cells. The cell uptake of chitosan-heparin polyplexes was equal to that of chitosan polyplexes, but heparin increased the transfection efficiency of the polyplexes two-fold. The application of chitosan-heparin small interfering RNA (siRNA) targeted to vascular endothelial growth factor (VEGF) silencing of ARPE-19 cells was 25% higher. Overall, chitosan-heparin polyplexes showed a significant improvement of gene release inside the cells, transfection, and gene silencing efficiency in vitro, suggesting that this fundamental strategy can further improve the transfection efficiency with application of non-viral vectors.

pH-sensitive chitosan DNA heparin transfection cytotoxicity


Simulation-based training for prostate biopsies: towards the validation of the Biopsym simulator.

Abstract: Objectives: The Biopsym simulator, a virtual-reality simulator for prostate biopsies, was designed to offer enhanced teaching of the biopsy procedure. The objectives of the present article are to describe the new version of the simulator and report the results of a new validation study.Material and methods: A prospective validation study was conducted between January and March 2017. The new version of the simulator, with improved physical realism, ultrasound image deformation, and a new scoring system, was evaluated by novice and confirmed users.Results: Twenty-one users evaluated the simulator, including ten novices and 11 confirmed users. The overall realism of the biopsy procedure was rated at 7.7/10 (IQR 5.7-9). The differences between the rates given by confirmed users and novices were not statistically significant. The median overall score obtained for the performance of 12 systematic ultrasound-guided biopsies was 43% (IQR 33-55). The median score obtained by confirmed users was 54% (IQR 46-62), and the median score obtained by novices was 31% (IQR 20-35). The difference between the scores was statistically significant (p = 0.005).Conclusions: This study allowed us to gather evidence towards the validation, and particularly towards the construct validation of the new version of the Biopsym simulator.

prostate
biopsy
Simulation
computer-assisted training
surgery


Tobacco policies and on-premise smoking in bars and clubs that cater to young African Americans following the Maryland Clean Indoor Air Act of 2007.

Abstract: African American young adults ages 18-25 smoke less than their Caucasian peers, yet the burden of tobacco-related illness is significantly higher in African Americans than in Caucasians across the lifespan. Little is known about how clean indoor air laws affect tobacco smoking among African American young adults. We conducted a systematic observation of bars and clubs with events targeted to African American adults 18-25 in Baltimore City at two timepoints (October and November of 2008 and 2010) after enforcement of the Maryland Clean Indoor Air Act (CIAA). Twenty venues-selected on the basis of youth reports of popular venues-were rated during peak hours. All surveillance checklist items were restricted to what was observable in the public domain. There was a significant decrease in observed indoor smoking after CIAA enforcement. Observed outdoor smoking also decreased, but this change was not significant. Facilities for smoking outdoors increased significantly. The statewide smoking ban became effective February 1, 2008, yet measurable changes in smoking behavior in bars were not evident until the City engaged in stringent enforcement of the ban several months later.

Nesoff|Elizabeth D|ED|
Milam|Adam J|AJ|
Bone|Lee R|LR|
Stillman|Frances A|FA|
Smart|Mieka J|MJ|
Hoke|Kathleen S|KS|
Furr-Holden|C Debra M|CDM|

tobacco
African Americans
young adults
smoking ban


Impact of health belief modification on intention to make smoke free home among pregnant women.

Abstract:
BACKGROUND
This study examined the effects of health education on modification of health belief and intention among pregnant women to have smoke free home.

METHODS
In this randomized controlled study, 91 pregnant women completed the study in two groups. Intervention group was educated about the harms of environmental tobacco smoke (ETS) exposure. The Health Belief Model (HBM) was a framework for analyzing the beliefs. After 10-12 weeks, the HBM constructs and weekly ETS exposure at home were compared between the two groups.

RESULTS
After performing educational program, the subjects in intervention group perceived more susceptibility and severity and reported lower weekly ETS exposure at home than subjects in control group; but, the self efficacy and perceived barrier were not different. The relationships between HBM constructs and weekly ETS exposure were significant; but, there was no significant difference in point prevalence of having smoke free home.

CONCLUSIONS
This study indicated that the health education about ETS exposure can modify health belief and reduce EST exposure among pregnant women, but cannot affect the self efficacy and perceived barrier. To have smoke free home, they need to increase their self efficacy.

Kazemi|Ashraf|A|
Ehsanpour|Soheila|S|
Zahraei|Nafiseh Sadat Nekoei|NS|
Hasanzadeh|Akbar|A|
Beigi|Nastaran Mohammad Ali|NM|
Malverdi|Zahra|Z|

pregnant women
Health belief model
environmental tobacco smoke exposure


A recombinant subunit vaccine for bovine RSV and Histophilus somni protects calves against dual pathogen challenge.

Abstract: Bovine respiratory syncytial virus (BRSV) and Histophilus somni synergize to cause respiratory disease in cattle. These pathogens cause enhanced disease during dual-infection and an IgE response to antigens of H. somni in dual-infected but not singly infected calves. Vaccines containing whole inactivated BRSV or H. somni have been associated with IgE responses A vaccine strategy that avoids stimulation of IgE antibodies would provide superior protection from dual infection. We hypothesized that a subunit vaccine consisting of the nucleoprotein (NP) from BRSV and the recombinant antigen IbpA DR2 (a surface antigen of H. somni with two toxic fic motifs) in Quil A adjuvant would elicit protection without disease enhancement. Three groups of calves were vaccinated twice with either: Formalin inactivated BRSV (FI) plus Somnivac®, NP & IbpA DR2 plus Quil A or Quil A alone, followed by BRSV and H. somni challenge. Clinical scores and antibody levels (to whole pathogens and to the subunits) were evaluated. Lungs were examined at necropsy on day 23 after infection. Clinical scores were significantly greatest for the FI & Somnivac® group and both clinical scores and lung pathology were lowest for the subunit group. All calves shed BRSV in nasal secretions. FI & Somnivac® induced IgE antibodies to H. somni and BRSV, but not to NP or DR2. The subunit vaccine did not induce an IgE antibody response to IbpA DR2 antigen and induced little IgE to H. somni. It did not induce an IgG antibody response to BRSV and H. somni, but stimulated production of IgG antibodies against the subunits. In summary, the subunit vaccine, consisting of the BRSV NP and H. somni IbpA DR2 in Quil A, protected against severe clinical signs and decreased lung pathology but did not prevent viral shedding. Importantly it prevented synergistic disease expression in response to dual infection.

Gershwin|Laurel J|LJ|
Behrens|Nicole E|NE|
McEligot|Heather A|HA|
Carvallo-Chaigneau|Francisco R|FR|
Crum|Lauren T|LT|
Gunnarson|Brianna M|BM|
Corbeil|Lynette B|LB|

D018357:Respiratory Syncytial Virus Infections

Subunit
Vaccine
Histophilus somni
BRSV
IgE
Nucleoprotein


A Comparison of the Effects of Lung Protective Ventilation and Conventional Ventilation on Thermoregulation During Anaesthesia.

Abstract:
Objective
During prolonged surgery, hypothermia is an unwanted condition that frequently develops and increases complication rates. It has been shown that positive end-expiratory pressure (PEEP) during mechanical ventilation reduces hypothermia development by providing earlier peripheral vasoconstriction. In the present study, an investigation was made of the effect of two different ventilation models on perioperative hypothermia development.

Methods
A total of 40 patients undergoing elective lumbar disc surgery were randomised to either the conventional group (Group C, n=20, tidal volume=10 mL kg-1, PEEP=0 cm H2O) or the lung protective ventilation group (Group P, n=20, tidal volume=6 mL kg-1, PEEP=5 cm H2O). Demographic data on gender, age, weight, height, preoperative-postoperative temperatures and haemodynamic values were recorded. The point where the forearm to fingertip skin temperature difference reached 0°C was determined as the peripheral vasoconstriction development. At this point, the core temperature was recorded as the thermoregulatory vasoconstriction threshold.

Results
Demographic characteristics of the patients and haemodynamic variables were similar between the groups. Preoperative and postoperative temperature gradients were not significantly different between the two groups (p=0.827). There was also no significant difference between the two groups in respect of the vasoconstriction threshold of the patients (p=0.432).

Conclusion
The study results showed that lung protective ventilation has no advantage in preserving the perioperative core temperature compared to conventional ventilation.

Lung protective ventilation
thermoregulation
vasoconstriction threshold


Initial curing characteristics of composite cements under ceramic restorations.

Abstract:
PURPOSE
To assess the degree of conversion (DC) of dual-curing composite cements when cured through ceramic-veneered zirconia disks.

METHODS
Portions of mixed cement, either G-CEM LinkForce (GC), Panavia V5 (Kuraray Noritake) or ResiCEM (Shofu), were placed on the ATR crystal of a Fourier Transform Infrared Spectroscope (FTIR; iS50, Thermo Scientific) and squeezed to a 100-µm film thickness using a microscopy cover glass. DC (%) of the composite cements applied in self-curing mode was measured in the dark at 37°C. Following the dual-curing mode, the cements were light-cured directly (positive control) or through a ceramic-veneered zirconia disk (0.5-mm thick zirconia with a 1.0-mm thick veneering ceramic) for 40 sec using two light-curing units (G-Light Prima 2, GC; PenCure, Morita). Per experimental group, 5 tests were conducted to measure DC in self-cure and dual-cure mode (n=5). FTIR spectra of the composite cement films were acquired to determine DC every min up to 30 min. DC of the composite cements was statistically compared using two-way repeated-measures ANOVA (α=0.05).

RESULTS
For all cements investigated, the self-curing mode resulted in significantly lower DC at 10, 20 and 30 min than the light-curing mode. When the composite cements were light-cured through the zirconia disk, DC at 30 min dropped significantly for ResiCem (Shofu), while not for Panavia V5 (Kuraray Noritake) and G-CEM LinkForce (GC).

CONCLUSIONS
Self-curing slows down polymerization but does not reach for all composite cements the highest (light-cured) DC. Ceramic-veneered zirconia-based restorations may affect DC of some composite cements.

Inokoshi|Masanao|M|
Nozaki|Kosuke|K|
Takagaki|Tomohiro|T|
Okazaki|Yohei|Y|
Yoshihara|Kumiko|K|
Minakuchi|Shunsuke|S|
Van Meerbeek|Bart|B|

D055115:Light-Curing of Dental Adhesives

Degree of conversion
Zirconia
Light-curing unit
FTIR, Light spectrometer
Luting composite


Parechovirus A Detection by a Comprehensive Approach in a Clinical Laboratory.

Abstract: Parechovirus A (Human parechovirus, HPeV) causes symptoms ranging from severe neonatal infection to mild gastrointestinal and respiratory disease. Use of molecular approaches with RT-PCR and genotyping has improved the detection rate of HPeV. Conventional methods, such as viral culture and immunofluorescence assay, together with molecular methods facilitate comprehensive viral diagnosis. To establish the HPeV immunofluorescence assay, an antibody against HPeV capsid protein VP0 was generated by using antigenic epitope prediction data. The specificity of the anti-HPeV VP0 antibody was demonstrated on immunofluorescence assay, showing that this antibody was specific for HPeV but not enteroviruses. A total of 74 HPeV isolates, 7 non⁻polio-enteroviruses and 12 HPeV negative cell culture supernatant were used for evaluating the efficiency of the anti-HPeV VP0 antibody. The sensitivity of HPeV detection by the anti-HPeV VP0 antibody was consistent with 5'untranslated region (UTR) RT-PCR analysis. This study established comprehensive methods for HPeV detection that include viral culture and observation of cytopathic effect, immunofluorescence assay, RT-PCR and genotyping. The methods were incorporated into our routine clinical practice for viral diagnosis. In conclusion, this study established a protocol for enterovirus and HPeV virus identification that combines conventional and molecular methods and would be beneficial for HPeV diagnosis.

D019085:Fluorescent Antibody Technique, Direct

D060888:Real-Time Polymerase Chain Reaction

clinical laboratory
human parechovirus
immunofluorescence assay
emerging virus
virus diagnosis


Potent Cytotoxicity of Novel L-Shaped Ortho-Quinone Analogs through Inducing Apoptosis.

Abstract: Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds TB1, TB3, TB4, TB6, TC1, TC3, TC5, TC9, TC11, TC12, TC14, TC15, TC16, and TC17 exhibited a better broad-spectrum cytotoxicity on three cancer cells. TB7 and TC7 selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that TB3, TC1, TC3, TC7, and TC17 could significantly induce the apoptosis of PC3 cells. TC1 and TC17 significantly induced apoptosis of K562 cells. TC1, TC11, and TC14 induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.

Li|Sheng-You|SY| Sun|Ze-Kun|ZK| Zeng|Xue-Yi|XY| Zhang|Yue|Y| Wang|Meng-Ling|ML| Hu|Sheng-Cao|SC| Song|Jun-Rong|JR| Luo|Jun|J| Chen|Chao|C|0000-0002-0378-0589 Luo|Heng|H| Pan|Wei-Dong|WD|

D004354:Drug Screening Assays, Antitumor

ortho-quinones
antitumor activity
beta-lapachone
tanshione IIA


Melanoma Detection and Classification using Computerized Analysis of Dermoscopic Systems: A Review.

Abstract: Malignant melanoma is considered as one of the most deadly cancers, which has broadly increased worldwide since the last decade. In 2018, around 91,270 cases of melanoma were reported and 9,320 people died in the US. However, diagnosis at the initial stage indicates a high survival rate. The conventional diagnostic methods are expensive, inconvenient and subject to the dermatologist's expertise as well as a highly equipped environment. Recent achievements in computerized based systems are highly promising with improved accuracy and efficiency. Several measures such as irregularity, contrast stretching, change in origin, feature extraction and feature selection are considered for accurate melanoma detection and classification. Typically, digital dermoscopy comprises four fundamental image processing steps including preprocessing, segmentation, feature extraction and reduction, and lesion classification. Our survey is compared with the existing surveys in terms of preprocessing techniques (hair removal, contrast stretching) and their challenges, lesion segmentation methods, feature extraction methods with their challenges, features selection techniques, datasets for the validation of the digital system, classification methods and performance measure. Also, a brief summary of each step is presented in the tables. The challenges for each step are also described in detail, which clearly indicate why the digital systems are not performing well. Future directions are also given in this survey.

Nasir|Muhammad|M|
Khan|Muhammad Attique|MA|
Sharif|Muhammad|M|
Javed|Muhammad Younus|MY|
Saba|Tanzila|T|
Ali|Hashim|H|
Tariq|Junaid|J|

melanoma
classification
cancer
feature extraction
segmentation
Skin lesion


How prepared are Nigerian schools for ebola virus disease prevention and control?

Abstract:
BACKGROUND
Nigeria was one of the West African countries gripped by the fear of the spread of the Ebola virus disease (EVD), leading to a long period of delay in resumption of primary and secondary schools for academic activities in September 2014. The aim of this study was to assess the preparedness of schools in the north central region of Nigeria toward EVD prevention and control within 1 month of resumption of schools.

METHODS
This was a descriptive cross-sectional study among 76 schools selected using a multistage sampling method. Research instruments were self-administered, semi-structured questionnaires. Data was analyzed using the SPSS software version 17.0.

FINDINGS
Half (38) of the schools reported that some of the children could have traveled to EVD-infected areas during the holiday period; 77.6% (59) had their teachers formally trained on EVD prevention and control before resumption; 50% (38) set up a committee on EVD prevention; and 62.9% (63) carried out awareness-raising activities on school assembly ground. Based on some preventive measures criteria, 55.2% (42) were categorized ready, whereas 44.7% (34) were not ready for EVD prevention and control within 1 month of resumption of students back to school. About 76.3% (58) said they would like to sustain these EVD prevention efforts; 14.5% (11) would like to sustain such efforts at least until the end of the present term. Determinants of readiness for EVD prevention and control include being a private school, being an urban school, belief that children could have traveled to an EVD-infected area, and school having standard operating procedure or policy guidelines on EVD prevention and control.

CONCLUSION
The persistent call for postponement of school resumption might have been due to the unpreparedness of many of schools to meet EVD prevention and control guidelines. Schools need to take more proactive and sustainable measures toward effective control of the ongoing epidemic and prevention of future occurrences.

schools
Ebola virus disease
prevention and control
preparedness


Scolytodes Ferrari (Coleoptera, Scolytinae) from Ecuador: 40 new species, <br />and a molecular phylogenetic guide to infer species differences.

Abstract: The genus Scolytodes Ferrari is a highly diverse group of Neotropical bark beetles. Recent collecting by hand and canopy fogging in Ecuador produced many new records. Overlap in species composition between samples from the canopy and the ground was very low, and canopy fogging revealed the highest proportion of undescribed species. Altogether we report records for 55 species of Scolytodes from Ecuador, including 40 species new to science: Scolytodes pseudoatratus Jordal and Smith, sp. nov., Scolytodes latipes Jordal and Smith, sp. nov., Scolytodes sloanae Jordal and Smith, sp. nov., Scolytodes samamae Jordal and Smith, sp. nov., Scolytodes otongae Jordal and Smith, sp. nov., Scolytodes chaplini Jordal and Smith, sp. nov., Scolytodes projectus Jordal and Smith, sp. nov., Scolytodes lubricus Jordal and Smith, sp. nov., Scolytodes inordinatus Jordal and Smith, sp. nov., Scolytodes cancellatus Jordal and Smith, sp. nov., Scolytodes jubatus Jordal and Smith, sp. nov., Scolytodes abbreviatus Jordal and Smith, sp. nov., Scolytodes stramineus Jordal and Smith, sp. nov., Scolytodes teres Jordal and Smith, sp. nov., Scolytodes animus Jordal and Smith, sp. nov., Scolytodes pseudoanimus Jordal and Smith, sp. nov., Scolytodes bombycinus Jordal and Smith, sp. nov., Scolytodes bisetosus Jordal and Smith, sp. nov., Scolytodes horridus Jordal and Smith, sp. nov., Scolytodes virgatus Jordal and Smith, sp. nov., Scolytodes criniger Jordal and Smith, sp. nov., Scolytodes pseudocrassus Jordal and Smith, sp. nov., Scolytodes semicrassus Jordal and Smith, sp. nov., Scolytodes pseudolepidus Jordal and Smith, sp. nov., Scolytodes semilepidus Jordal and Smith, sp. nov., Scolytodes fortis Jordal and Smith, sp. nov., Scolytodes peniculus Jordal and Smith, sp. nov., Scolytodes tristis Jordal and Smith, sp. nov., Scolytodes chrysifrons Jordal and Smith, sp. nov., Scolytodes amictus Jordal and Smith, sp. nov., Scolytodes cnesinoides Jordal and Smith, sp. nov., Scolytodes maestus Jordal and Smith, sp. nov., Scolytodes vietus Jordal and Smith, sp. nov., Scolytodes echinus Jordal and Smith, sp. nov., Scolytodes rufifrons Jordal and Smith, sp. nov., Scolytodes arcuatus Jordal and Smith, sp. nov., Scolytodes validus Jordal and Smith, sp. nov., Scolytodes sparsus Jordal and Smith, sp. nov., Scolytodes lapillus Jordal and Smith, sp. nov., Scolytodes coronatus Jordal and Smith, sp. nov. We also provide the first description of the female and a new country record for Scolytodes grandis (Schedl, 1962) (=Scolytodes glaberrimus Wood, 1972 syn. nov.) and a redescription and new country record for Scolytodes pilifrons (Schedl, 1962). The total number of valid species is now 287. Additional new country records were established for Scolytodes acuminatus Wood, 1969, Scolytodes comosus Jordal and Kirkendall, 2019, Scolytodes costabilis Wood, 1974, Scolytodes glabrescens Wood, 1972, Scolytodes impressus Wood, 1969, Scolytodes nitidus (Eggers, 1928), Scolytodes striatus (Eggers, 1934), Scolytodes tucumani Wood, 2007, and from another Hexacolini genus, Pycnarthrum fulgidum Wood, 1977. The first molecular phylogeny for Scolytodes is provided and used primarily to guide the inference of species validity. Molecular data from COI, 28S and EF-1α revealed substantial genetic divergence between morphologically very similar but diagnosable species.

Coleoptera, 28S, canopy fogging, COI, Ecuador, EF-1α, molecular phylogeny, Scolytodes


Arrhythmias in dilated cardiomyopathy.

Abstract: Patients with dilated cardiomyopathies (DCM) face a significant burden of arrhythmias, including conduction defects such as atrioventricular block and interventricular delay in the form of left bundle branch block, resulting in altered electromechanical coupling that can exacerbate heart failure. Atrial fibrillation is common and carries an adverse prognosis. Ventricular arrhythmias and sudden cardiac death generally occur late in the disease course. Sustained monomorphic ventricular tachycardia accounts for most of the sustained ventricular arrhythmias in DCM. This article summarizes common forms of arrhythmias encountered in patients with DCM, and reviews the relevant electrophysiologic basis of these arrhythmias and their management.

Kumar|Saurabh|S|
Stevenson|William G|WG|
John|Roy M|RM|

D001145:Arrhythmias, Cardiac
D002311:Cardiomyopathy, Dilated
D017115:Catheter Ablation
D006801:Humans

Dilated cardiomyopathy
Atrioventricular block
Atrial fibrillation
Ventricular tachycardia
Atrial flutter
Catheter ablation
Lamin A/C cardiomyopathy


Effects of tapering on neuromuscular and metabolic fitness in team sports: a systematic review and meta-analysis.

Abstract: Purpose: To assess the effects of a taper strategy on neuromuscular and metabolic fitness in team sport athletes, through a systematic review and meta-analysis. Method: To be included in this meta-analysis, studies had to involve competitive team sport athletes and a tapering intervention providing details about the procedures used to decrease the training load, as well as competition or field-based criterion performance and all necessary data to calculate effect sizes. Four databases were searched according to these criteria, which led to the identification of 895 potential studies and the subsequent inclusion of 14 articles. Independent variables were training intensity, volume and frequency, as well as the pattern of taper and its duration. The dependent variable was performance obtained in various neuromuscular and metabolic tests. Results: There was limited evidence of a moderate taper-induced improvement in repeated sprint ability (Standardized Mean Difference (SMD) (95%IC;I2) = 0.41 (0.26-0.55;0%)) and moderate evidence of a moderate increase in maximal power (SMD (95%IC;I2) = 0.44 (0.32-0.56;15%)), change of direction speed (SMD (95%IC;I2) = 0.38 (0.15-0.60;28%)) and maximal oxygen uptake (SMD (95%IC;I2) = 0.76 (0.43-1.09;37%)). Conclusion: Tapering is an effective training strategy to improve maximal power, maximal oxygen uptake, repeated sprint ability and change of direction speed in team sports. However, the literature lacks studies using various tapering strategies to compare their effectiveness and make evidence-based recommendations. Future original studies should focus on this major issue.

D000222:Adaptation, Physiological
D000223:Adaptation, Psychological
D056352:Athletes
D054874:Athletic Performance
D016001:Confidence Intervals
D006801:Humans
D009068:Movement
D053580:Muscle Strength
D010101:Oxygen Consumption
D064797:Physical Conditioning, Human
D012420:Running
D000085944:Team Sports
D013997:Time Factors

Team sport
training load
repeated sprint ability
maximal power
change of direction
maximal oxygen uptake


Regenerative effect of mesenteric fat stem cells on ccl4-induced liver cirrhosis, an experimental study.

Abstract:
Background
Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model.

Methods
Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma.

Results
After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies.

Conclusion
Liver cirrhosis was induced. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status of the rats, as cirrhotic livers were regenerated back into normal appearing parenchyma. Rats' clinical behavior also reached healthy status.

Nazhvani|Fatemeh Dehghani|FD|
Haghani|Iman|I|
Nazhvani|Seifollah Dehghani|SD|
Namazi|Fatemeh|F|
Ghaderi|Abbas|A|

ADSCs, Multipotent adipose-derived stem cells

VEGF, Vascular endothelial growth factor


Macrophage polarization in health and disease.

Abstract: Macrophages are terminally differentiated cells of the mononuclear phagocyte system that also encompasses dendritic cells, circulating blood monocytes, and committed myeloid progenitor cells in the bone marrow. Both macrophages and their monocytic precursors can change their functional state in response to microenvironmental cues exhibiting a marked heterogeneity. However, there are still uncertainties regarding distinct expression patterns of surface markers that clearly define macrophage subsets, particularly in the case of human macrophages. In addition to their tissue distribution, macrophages can be functionally polarized into M1 (proinflammatory) and M2 (alternatively activated) as well as regulatory cells in response to both exogenous infections and solid tumors as well as by systems biology approaches.

macrophage
polarization
tumors
HIV
M1/M2
TAMs (tumor-associated macrophages)
regulatory macrophages


Levels of Serum Calcium and Magnesium in Pre-eclamptic and Normal Pregnancy: A Study from Coastal India.

Abstract:
BACKGROUND
Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. Though the aetiology is obscure, recent studies indicate that serum levels of calcium and magnesium may have a role in pre-eclampsia.

AIM
The aim of this study was to find out the relationship of serum levels of calcium and magnesium in pre-eclamptic pregnancies compared to normal pregnancies in women from southern coastal India.

SETTINGS AND DESIGN
This study was done in a medical college hospital in southern coastal India.

MATERIALS AND METHODS
The blood samples from 60 pre-eclamptic women and an equal number of controls were analysed for calcium and magnesium levels. Data on Body Mass Index, maternal and gestational ages, serum calcium and magnesium were compared between the two groups. Outcome of pregnancy was analysed in both the groups and compared.

STATISTICAL ANALYSIS
Data was expressed as Mean ± Standard Deviation. Data analysis was done by SPSS version 20. Comparison of serum levels of the elements between the two groups was performed by Independent t-test and Chi-square test and P-value of < 0.05 was considered as statistically significant.

RESULTS
The serum calcium concentration was significantly lower in the pre-eclamptic group compared to normotensives (7.84 ± 0.87 mg/dl Vs 8.97± 0.69 mg/dl, p<0.001) whereas the levels of serum magnesium showed a marginal difference in both the groups. (1.43± 0.55 mg/dl Vs, 1.57 ± 0.72 mg/dl P 0.257) The study also showed that pre-eclamptic women were older, their BMI was higher and birth weight of babies lower compared to normotensives.

CONCLUSION
According to the results of our research, intake of supplements, mainly calcium may help in the reduction of incidence of pre-eclampsia especially in a population of a developing country like ours where the nutrition is poor. Not many studies have been done in developing countries to assess the role of these elements in pre-eclampsia. The actual role of magnesium and calcium supplements needs further investigation.

Kanagal|Deepa V|DV|
Rajesh|Aparna|A|
Rao|Kavyarashmi|K|
Devi|Ullal Harshini|UH|
Shetty|Harish|H|
Kumari|Sucheta|S|
Shetty|Prasanna Kumar|PK|

Calcium Magnesium Pre-eclampsia Nutrition


A reliable phenotypic assay for detection of ESBLs and AmpCs in MBL-producing gram-negative bacteria with the use of aminophenylboronic acid, dipicolinic acid and cloxacillin.

Abstract: ESBLs and AmpCs may escape detection when they coexist with metallo-β-lactamases such as New Delhi Metallo-β-lactamases-1. In this study a combination disk assay was established using cefotaxime, cefotaxime/clavulanic acid, cefotaxime/clavulanic acid/cloxacillin, cefoxitin and cefoxitin/phenylboronic acid/cloxacillin on Mueller Hinton agar supplemented with dipicolinic acid for determination of β-lactamases in the presence of NDM-1.

Datta|Saswati|S| Chatterjee|Somdatta|S| Mitra|Shravani|S| Basu|Sulagna|S|

Gram-negative bacteria
Dipicolinic acid
Cloxacillin
Phenylboronic acid
NDM-1
Combination disk test


Crystal structure and spectroscopic characterization of a cobalt(II) tetraazamacrocycle: completing a series of first-row transition-metal complexes.

Abstract: The tetraazamacrocyclic ligand 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (TMC) has been used to bind a variety of first-row transition metals but to date the crystal structure of the cobalt(II) complex has been missing from this series. The missing cobalt complex chlorido(1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane-κ4N)cobalt(II) chloride dihydrate, [CoCl(C14H32N4)]Cl·2H2O or [CoIICl(TMC)]Cl·2H2O, crystallizes as a purple crystal. This species adopts a distorted square-pyramidal geometry in which the TMC ligand assumes the trans-I configuration and the chloride ion binds in the syn-methyl pocket of the ligand. The CoII ion adopts an S = 3/2 spin state, as measured by the Evans NMR method, and UV-visible spectroscopic studies indicate that the title hydrated salt is stable in solution. Density functional theory (DFT) studies reveal that the geometric parameters of [CoIICl(TMC)]Cl·2H2O are sensitive to the cobalt spin state and correctly predict a change in spin state upon a minor perturbation to the ligand environment.

Van Heuvelen|Katherine M|KM|
Lee|Isabell|I|
Arriola|Katherine|K|
Griffin|Rilke|R|
Ye|Christopher|C|
Takase|Michael K|MK|

crystal structure
tetraazamacrocycle
density functional theory
UV–visible spectroscopy
computational chemistry
divalent cobalt


Towards a Functional Cure for Diabetes Using Stem Cell-Derived Beta Cells: Are We There Yet?

Abstract: Diabetes mellitus is a pandemic metabolic disorder that results from either the autoimmune destruction or the dysfunction of insulin-producing pancreatic beta cells. A promising cure is beta cell replacement through the transplantation of islets of Langerhans. However, donor shortage hinders the widespread implementation of this therapy. Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, represent an attractive alternative beta cell source for transplantation. Although major advances over the past two decades have led to the generation of stem cell-derived beta-like cells that share many features with genuine beta cells, producing fully mature beta cells remains challenging. Here, we review the current status of beta cell differentiation protocols and highlight specific challenges that are associated with producing mature beta cells. We address the challenges and opportunities that are offered by monogenic forms of diabetes. Finally, we discuss the remaining hurdles for clinical application of stem cell-derived beta cells and the status of ongoing clinical trials.

D002454:Cell Differentiation
D003922:Diabetes Mellitus, Type 1
D000066449:Human Embryonic Stem Cells
D006801:Humans
D057026:Induced Pluripotent Stem Cells
D050417:Insulin-Secreting Cells


Improvement of the Physical Properties of Guided Bone Regeneration Membrane from Porcine Pericardium by Polyphenols-Rich Pomace Extract.

Abstract: To achieve optimal performances, guided bone regeneration membranes should have several properties, in particular, proper stiffness and tear resistance for space maintenance, appropriate resorption time, and non-cytotoxic effect. In this work, polyphenol-rich pomace extract (PRPE), from a selected grape variety (Nebbiolo), rich in proanthocyanidins and flavonols (e.g., quercetin), was used as a rich source of polyphenols, natural collagen crosslinkers, to improve the physical properties of the porcine pericardium membrane. The incorporation of polyphenols in the collagen network of the membrane was clearly identified by infra-red spectroscopy through the presence of a specific peak between 1360-1380 cm-1. Polyphenols incorporated into the pericardium membrane bind to collagen with high affinity and reduce enzymatic degradation by 20% compared to the native pericardium. The release study shows a release of active molecules from the membrane, suggesting a possible use in patients affected by periodontitis, considering the role of polyphenols in the control of this pathology. Mechanical stiffness is increased making the membrane easier to handle. Young's modulus of pericardium treated with PRPE was three-fold higher than the one measured on native pericardium. Tear and suture retention strength measurement suggest favorable properties in the light of clinical practice requirements.

guided bone regeneration
membrane
porcine pericardium
polyphenols
antioxidant
biomaterial


Effect of pomegranate peel extract on the oxidative stability of pomegranate seed oil.

Abstract: Pomegranate seed oil is valuable source of bioactive compounds with health-beneficial effects, but it is sensitive to oxidation due to high content of PUFA. In order to improve stability of pomegranate seed oil, the influence of natural antioxidant (0.1% pomegranate peel extract) and a combination of synthetic antioxidant (0.01% butylhydroxytoluene) and pomegranate peel extract (0.05%) was investigated. The oxidation process was followed by monitoring fatty acid composition and measuring the quality and stability parameters of oil (acid value, peroxide value, anisidine value and thiobarbituric acid reactive substances value) during storage for 12 days at 65 ⁰C. Furthermore, total phenolic content and DPPH radical scavenging activity was measured. Pomegranate peel extract as well as a combination of pomegranate peel extract and BHT can have a significant positive impact (P < 0.05) on improvement of the quality and stability parameters of pomegranate seed oil. Furthermore, such activity was better than BHT used alone.

Drinić|Zorica|Z| Mudrić|Jelena|J| Zdunić|Gordana|G| Bigović|Dubravka|D| Menković|Nebojša|N| Šavikin|Katarina|K|

D017392:Thiobarbituric Acid Reactive Substances

Pomegranate peel extract
Pomegranate seed oil
Peroxide value
P-anisidine value
Punicic acid
TBARS value


A fluorescent sensor recognized by the FA1 site for highly sensitive detection of HSA.

Abstract: Human serum albumin (HSA), as the most abundant protein in blood plasma, plays a crucial role in many physiological processes. The abnormal HSA level in serum or in urine is often associated with various diseases. Therefore, to achieve highly sensitive and selective quantification of HSA is of great importance for disease diagnosis and preventive medicine. Herein, an HSA-selective light-up fluorescent sensor, DCM-ML, was successfully developed for quantitative detection of HSA. DCM-ML exhibited good (photo-) stability and strong fluorescence enhancement around 630 nm in the presence of HSA in complex samples containing numerous biological analytes. Upon addition of HSA into DCM-ML containing solution, a good linear relationship (R2 > 0.99) between the fluorescence intensity of DCM-ML and HSA concentration from 0 to 0.08 mg/mL was obtained with the detection limit of 0.25 μg/mL. The sensing mechanism of the sensor towards HSA was demonstrated to be via recognition in the fatty acid site 1 (FA1), instead of the most reported binding sites (Sudlow I and II) in HSA, for the first time, by both the displacement experiments and molecular docking simulation. Thus, DCM-ML can also be assumed as a potential FA1 site-binding marker for examining drugs binding to the FA1 site in HSA. At last, the utilization of sensor DCM-ML for quantification and validation of HSA in urine samples and cell culture medium was effectively demonstrated. Therefore, the development of DCM-ML should find great application potentials in the fields of analytical chemistry and clinical medicine as a highly sensitive HSA sensor.

Chao|Xijuan|X| Yao|Dezhi|D| Qi|Yongmei|Y| Yuan|Cong|C| Huang|Dejun|D|

D001665:Binding Sites
D005227:Fatty Acids
D006801:Humans
D062105:Molecular Docking Simulation
D011485:Protein Binding
D000075462:Serum Albumin, Human
D013050:Spectrometry, Fluorescence

Fluorescent sensor
FA1 site
HSA
Cell culture medium
Human urine


Nucleus N5 CI500 series implant recall: hard failure rate at a major Cochlear implantation center.

Abstract:
OBJECTIVES/HYPOTHESIS
To compare the cumulative failure percentage of the Cochlear Nucleus N5 CI500 series implant observed, both before and after the voluntary recall of unimplanted devices, to that of the Cochlear Nucleus Freedom CI24RE series implant.

STUDY DESIGN
Retrospective review of 411 patients implanted with either the Nucleus Freedom or the Nucleus N5 device.

METHODS
Cochlear implantation was performed in standard fashion. A database was created by combining information obtained from operative case logs, an integrated clinical electronic medical records system, and an external database of devices maintained by Cochlear Corporation.

RESULTS
Of the 289 implants of the Nucleus Freedom CI24RE series device at this institution, the cumulative failure percentage was 0%. There were 122 implants of the Nucleus N5 CI500 series device, yielding a 9.8% cumulative failure percent; 82 were manufactured before the voluntary recall and 40 were produced afterward. The 82 implants manufactured before the recall had two associated failures, while the 40 produced afterward had 10 failures.

CONCLUSIONS
It is possible that the cumulative failure percentage (CFP) of the Cochlear Nucleus N5 CI500 series implant is not fully defined. While the CFP of the Nucleus Freedom CI24RE series implant at this institution was 0%, it was 9.8% for the Nucleus N5. The CFP of Nucleus N5 devices manufactured before the voluntary recall was 2.4%, while the CFP afterward was 25.0%-nearly 6-fold higher than the company-published value of 4.2% for all Nucleus N5 implants registered globally.

Hildrew|Douglas M|DM|
Molony|Timothy B|TB|

Nucleus N5
recall
hard failure
Cochlear implant
cumulative failure percentage
Nucleus Freedom
CI24RE
CI512
diode
hermetic seal
hermeticity
microcrack


Cue-based and algorithmic learning in common carp: A possible link to stress coping style.

Abstract: Common carp that had been screened for stress coping style using a standard behavioural test (response to a novel environment) were given a learning task in which food was concealed in one of two compartments, its location randomised between trials and its presence in a given compartment signalled by either a red or a yellow light. All the fish learned to find food quickly, but did so in different ways. Fifty five percent learned to use the light cue to locate food; the remainder achieved the same result by developing a fixed movement routine. To explore this variation, we related learning strategy to stress coping style. Time to find food fell identically with successive trials in carp classified as reactive or proactive, but reactive fish tended to follow the light cue and proactive fish to adopt a fixed routine. Among fish that learned to follow the light, reactive individuals took fewer trials to reach the learning criterion than did proactive fish. These results add to the growing body of information on within-species variation in learning strategies and suggest a possible influence of stress coping style on the use of associative learning as opposed to algorithmic searching during foraging.

Mesquita|Flavia Oliveira|FO|
Borcato|Fabio Luiz|FL|
Huntingford|Felicity Ann|FA|

Common carp
Stress coping style
Association learning
Cyprinus carpio
Personality
Routine formation


Impact-Induced Muscle Damage: Performance Implications in Response to a Novel Collision Simulator and Associated Timeline of Recovery.

Abstract: The implications of impact-induced muscle damage (IIMD) that results from participation in contact-sport are not well understood. The purpose of the present study was to implement a novel method of generating IIMD and characterise the implications of this on perceptual, biochemical and exercise performance parameters. Eighteen male recreational contact-sport athletes completed a single-group time series with measures assessed at baseline (PRE) and immediately following (POST) an IIMD protocol, with repeat testing 24, 48, and 72 h following the IIMD protocol. Biochemical indices of muscle damage (myoglobin [Mb]) and inflammation (high-sensitivity C-reactive protein [hs-CRP]), 15 m sprint performance, squat jump peak power (SJ-PP), and perceived soreness were compared to PRE using a one-way (time) repeated measures ANOVA with post-hoc t tests. Speed over 5 and 15 m were impaired for 48 h (7.5 ± 4%, p < 0.01) and SJ-PP was impaired for 48 h following the IIMD protocol (9.5 ±3 %, p < 0.01). Subjective soreness was elevated from baseline for 72 h (P < 0.01) following the IIMD protocol. No change in [CRP] or [Mb] was observed (p > 0.01). IIMD resulted in impaired ability to produce power and speed, whilst negatively influencing perceived soreness. These changes were most pronounced in the 48 h following the IIMD protocol. No change in muscle damage or inflammation indices were observed, primarily due to the highly variable response. Thus, the experimental protocol used in the present study may be used as a model to further investigate other aspects of IIMD.

Naughton|Mitchell|M|
Miller|Joanna|J|
Slater|Gary J|GJ|

Muscle damage
performance
collisions
recovery
rugby


A nitric oxide-releasing hydrogel for enhancing the therapeutic effects of mesenchymal stem cell therapy for hindlimb ischemia.

Abstract: Therapeutic angiogenesis with mesenchymal stem cells (MSCs) is promising for the clinical treatment of peripheral artery disease (PAD). However, the heterogeneous proangiogenic nature of MSCs is a key challenge in developing more effective treatments with MSCs for therapeutic angiogenesis purposes. Here, we propose to enhance the therapeutic function of human placenta-derived MSCs (hP-MSCs) in hindlimb ischemia therapy by using nitric oxide (NO)-releasing chitosan hydrogel (CS-NO). Our data showed that the co-transplantation of CS-NO hydrogel with hP-MSCs remarkably improved the grafting of hP-MSCs and ameliorated the functional recovery of ischemic hindlimbs. Moreover, we found that the neovascularization of damaged hindlimbs was significantly increased after co-transplanting CS-NO hydrogel and hP-MSCs, as confirmed by bioluminescence imaging (BLI). Further analysis revealed an endothelial-like status transformation of hP-MSCs in the presence of NO, which was identified as a potential mechanism contributing to the enhanced endothelium-protective and proangiogenic capacities of hP-MSCs that promote angiogenesis in mouse models of hindlimb ischemia. In conclusion, this study provides a promising approach for using NO hydrogel to improve the proangiogenic potency of MSCs in ischemic diseases, and the strategy used here facilitates the development of controlled-release scaffolds for enhancing the therapeutic efficiency of MSCs in angiogenic therapy. STATEMENT OF SIGNIFICANCE: The heterogeneous proangiogenic nature of mesenchymal stem cells (MSCs) is a key challenge in developing more effective treatments with MSCs for therapeutic angiogenesis purposes. In this study, we investigated whether nitric oxide (NO)-releasing chitosan hydrogel (CS-NO) could improve the proangiogenic potency of MSCs in ischemic diseases. Our results revealed an endothelial-like status transformation of human placenta-derived MSCs (hP-MSCs) in the presence of NO, which was identified as a potential mechanism contributing to the enhanced endothelium-protective and proangiogenic capacities of hP-MSCs that promote angiogenesis in mouse models of hindlimb ischemia. The strategy for enhancing the pro-angiogenic activity of MSCs with biomaterials provides a practical idea for overcoming the challenges associated with the clinical application of MSCs in therapeutic angiogenesis.

Zhang|Kaiyue|K| Chen|Xiaoniao|X| Li|Huifang|H| Feng|Guowei|G| Nie|Yan|Y| Wei|Yongzhen|Y| Li|Nana|N| Han|Zhibo|Z| Han|Zhong-Chao|ZC| Kong|Deling|D| Guo|Zhikun|Z| Zhao|Qiang|Q| Li|Zongjin|Z|

D045164:Mesenchymal Stem Cell Transplantation

Hydrogel
Mesenchymal stem cells
Hindlimb ischemia
Angiogenesis
Nitric oxide
Bioluminescence imaging (BLI)
Endothelial cells


A temporally sustained implicit theory of mind deficit in autism spectrum disorders.

Abstract: Eye movements during false-belief tasks can reveal an individual's capacity to implicitly monitor others' mental states (theory of mind - ToM). It has been suggested, based on the results of a single-trial-experiment, that this ability is impaired in those with a high-functioning autism spectrum disorder (ASD), despite neurotypical-like performance on explicit ToM measures. However, given there are known attention differences and visual hypersensitivities in ASD it is important to establish whether such impairments are evident over time. In addition, investigating implicit ToM using a repeated trial approach allows an assessment of whether learning processes can reduce the ASD impairment in this ability, as is the case with explicit ToM. Here we investigated the temporal profile of implicit ToM in individuals with ASD and a control group. Despite similar performance on explicit ToM measures, ASD-diagnosed individuals showed no evidence of implicit false-belief tracking even over a one-hour period and many trials, whereas control participants did. These findings demonstrate that the systems involved in implicit and explicit ToM are distinct and hint that impaired implicit false-belief tracking may play an important role in ASD. Further, they indicate that learning processes do not alleviate this impairment across the presentation of multiple trials.

Schneider|Dana|D|
Slaughter|Virginia P|VP|
Bayliss|Andrew P|AP|
Dux|Paul E|PE|

D002659:Child Development Disorders, Pervasive

Implicit theory of mind
Autism spectrum disorders
Eye-movements
Social cognition


Cardiac Metastases in Patients with Neuroendocrine Tumours: Clinical Features, Therapy Outcomes, and Prognostic Implications.

Abstract:
BACKGROUND
Cardiac metastases (CM) from neuroendocrine tumours (NET) are rare; however, with the introduction of new molecular imaging modalities, such as 68Ga-DOTATATE PET-CT for NET diagnosis and re-staging, they are now identified more frequently. This study presents a single-institution experience on the NET CM characteristics, management, and prognostic implications.

METHODS
Between January 1998 and January 2020, 25 NET patients with CM were treated in our unit. A retrospective review of electronic records was performed. Overall survival (OS) was assessed by the Kaplan-Meier method. Cox regression models were used to evaluate the association of various clinical variables with OS.

RESULTS
The median age in the NET CM cohort was 64 years, with small intestine being the most common primary (84%). Nearly half of the patients suffered either from shortness of breath (48%) or had palpitations (12%). Peptide receptor radionuclide therapy (PRRT) was applied in more than half of the patients (64%), who had an improved trend for a longer median OS compared to those patients who did not receive PRRT (76.0 vs. 14.0 months, p = 0.196). The multivariate analysis demonstrated that concomitant skeletal or pancreatic metastases, as well as N-terminal pro-B-type natriuretic peptide (NT pro-BNP) >2 × upper limit of normal (ULN), were independent poor prognosticators.

CONCLUSIONS
Clinical features of NET CM ranged from asymptomatic patients to heart failure. Concomitant bone or pancreatic metastases and NT pro-BNP levels >2 ULN predicted shorter survival time. PRRT serves as a feasible therapy with promising survival benefits; however, more data are needed.

Liu|Man|M|
Armeni|Eleni|E|
Navalkissoor|Shaunak|S|
Davar|Joseph|J|
Sullivan|Luke|L|
Leigh|Charlotte|C|
O'Mahony|Luke Furtado|LF|
Hayes|Aimee|A|
Mandair|Dalvinder|D|
Chen|Jie|J|
Caplin|Martyn|M|
Toumpanakis|Christos|C|

Cardiac metastases
Neuroendocrine tumours
Prognostic factors


Platelet glycoprotein VI genetic quantitative and qualitative defects.

Abstract: Platelet membrane glycoprotein VI (GPVI) is increasingly recognized as an important receptor for thrombus formation and growth. Numerous arguments have been published indicating that GPVI plays a major role in thrombosis without being essential for physiological hemostasis. In humans, GPVI deficiencies are rarely reported. These are most often deficiencies occurring in the context of autoimmunity and, more rarely, genetic deficits. The purpose of this review is to compile data on the quantitative and qualitative genetic abnormalities of GPVI.

D001792:Blood Platelets
D006801:Humans
D010980:Platelet Membrane Glycoproteins

Glycoprotein VI
genetic deficiency
platelet disorder


Susac syndrome and pregnancy: a review of published cases and considerations for patient management.

Abstract: Susac syndrome (SuS) is a rare autoimmune endotheliopathy leading to hearing loss, branch retinal artery occlusions and encephalopathy. Young females are more frequently affected than males, making counselling for family planning an important issue. We reviewed published cases on SuS during pregnancy or in the postpartum period, and selected 27 reports describing the details of 33 patients with SuS. Treatment options and implications for pregnancy and breastfeeding are discussed. We propose new areas for research and suggest a management strategy.


The species composition of thrips (insecta: thysanoptera) inhabiting mango orchards in pulau pinang, malaysia.

Abstract: A field study was conducted at two localities on Pulau Pinang, Malaysia, during two consecutive mango flowering seasons in 2009 to identify variations in the species composition of thrips infesting treated and untreated mango (Mangifera indica L.) orchards. The CO2 immobilisation technique and the cutting method were used to recover different thrips species from mango panicles and weed host plants, respectively. The mango panicles and various weed species within the treated orchard were found to harbour four thrips species from the family Thripidae. These species were identified as Thrips hawaiiensis (Morgan), Scirtothrips dorsalis (Hood), Frankliniella schultzei (Trybom) and Megalurothrips usitatus (Bagnall). The weed species Mimosa pudica, Cleome rutidosperma, Echinochloa colonum, Borreria laevicaulis, Veronia cinerea and Asystasia coromandeliana served as additional hosts to these thrips. Six thrips species were found in the untreated orchard. These species included Thrips palmi (Karny), Haplothrips sp. (Amyot and Serville) and the four thrips species found in the treated orchard. A brief description of the larvae for each genus is provided.

Aliakbarpour|Hamaseh|H|
Rawi|Che Salmah Md|CS|